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Regular inspection of tunnel surfaces is an important practice from both a safety and tunnel asset management perspective. However, inspection for cracking and spalling is still predominantly a manual task, which is time consuming, subjective, and exposes on-foot staff to risk. This presentation will explore the use of 3D laser scanning technology and artificial intelligence to automate the inspection process with a Canadian metro case study being presented.

Short films have proven an important medium for social commentary in contemporary Indonesia. As an example of the genre, this special issue of BKI presents Candra Aditya’s (2016) short film, Dewi pulang (Dewi goes home), which follows a young Javanese woman as she travels from Jakarta to her natal home in Central Java to attend her father’s funeral. A critically annotated transcript and translation of the film’s dialogue is followed by four essays on various aspects of the film and a conversation with the filmmaker. Issues addressed include the changing nature of short films and ‘indie’ cinema in post-authoritarian Indonesia; the filmmaking practices specific to Dewi pulang; the interplay of absence and presence in Dewi’s movement between Jakarta and her natal home in Central Java; and the juxtaposition of Indonesian-, English- and Javanese-language dialogue, and the forms of sociality they respectively embody. Taken as a whole, the special issue offers at once a window onto short filmmaking in Indonesia and new primary materials for further analysis.

Summary Background There is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. Methods The PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov , NCT04411784 . Findings We included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. Interpretation The COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes. Funding None.

The present article is a case study of a Polish biopharmaceutical company, “Pure Biologics”. The company was founded in 2010 by a group of scientists and, over the last nine years, grew substantially from just a few individuals to nearly one hundred professionals. Initially, a privately-funded civil partnership, Pure Biologics, has been transformed into a publicly-traded company. Such a transformation has been possible not only because of the expertise and growing experience of corporate management, but also the specific economic environment and substantial public funding dedicated to innovative Small and Medium Enterprises (SMEs).

Much recent scientific, media and public attention has focussed on the evidence for and consequences of declines in insect biodiversity. Reliable, complete inventories can be used to estimate insect trends accurately, but incomplete data may distort assessments of biodi-versity change. Thus, it is essential to understand the completeness of insect inventories. Assessing the database of Great Britain butterfly occurrences, likely the most complete database for any group of insects in the world (with 10,046,366 records for 58 butterfly species), we found that only 62% of the cells have complete inventories at the finest scale evaluated. The dynamic nature of butterfly distributions in response to climate change could explain this result, as the distribution of completeness values is related to the increas-ing occurrence of some species at higher latitudes as a consequence of recent range expan-sions. The exceptional quantity of information collected in Great Britain about this appeal-ing group of insects is insufficient to provide a complete picture. Consequently, we cannot expect to build complete inventories for less popular taxa, especially in less comprehen-sively sampled countries, and will require other techniques to understand the full extent of global biodiversity loss., D. S-F was supported by a postdoctoral grant from the University of Murcia (Spain).

1. The description of how biological information is compiled over time is essential to detect temporal biases in biodiversity data that could directly influence the utility, comparability, and reliability of ecological and biogeographical studies. 2. We explore trends in species recording over time using one of the most spatially and temporally comprehensive country-level databases for any group of insects in the world – the database of butterfly occurrences from Great Britain. 3. Firstly, we used two crucial milestones (the year in which the taxonomic inventory is complete, i.e., when the last species was recorded, the year in which all species are recorded together for the first time) to delimit threemain phases in the process of biodiversity recording (taxonomic, faunistic and exhaustive phases). Secondly, we aimed to quantify how far species features (attractiveness and detectability) influence the process of recording through time. 4. During the first stage of biodiversity compilation,when the main aim is to complete the taxonomic inventory (taxonomic period), entomologists tend to record attractive species more frequently. However, once the inventory is complete, particularly in the period during whichmore spatially and temporally comprehensive information about species distribution is amassed (the exhaustive period), the recording pattern clearly changes to more detectable species. 5. Common, highly detectable species are undersampled in the first phase of biodiversity data compilation and oversampled in the final stages. Awareness of such temporal patterns in recording is necessary in order to correctly interpret and address bias in insect biodiversity trends

Introduction Endoscopic stapes surgery is a technically demanding procedure that is increasing in popularity. Surgical outcomes and complication rates have been demonstrated to be comparable to traditional microscopic techniques. The surgical outcomes for patients undergoing stapes surgery performed by the Sydney Endoscopic Ear Surgery Research Group are presented. Study design Retrospective review from prospectively gathered database. Setting Tertiary referral centers. Patients A retrospective case review of patients undergoing endoscopic stapes surgery performed by four surgeons between February 2015 and July 2019 was carried out. Sixty nine patients were identified, and assessed for demographics, functional results, and postoperative complications. Intervention Endoscopic stapedotomy. Main outcome measure Postoperative hearing results. Results Sixty eight of 69 patients (98.6%) achieved an air-bone gap (ABG) closure of less than 20 dB. Sixty of 69 patients (87%) achieved and ABG closure of less than 10 dB. The average improvement of the ABG over four frequencies achieved was 26.5 dB (range, 0-61). Postoperative complications were infrequent and self-limiting. Six patients experienced dysgeusia without obvious chorda tympani injury, four patients developed short lived vertigo, and two patients experienced tinnitus. Conclusions Endoscopically assisted stapes surgery represents a safe alternative to traditional microscopic techniques, with similar morbidity and audiological outcomes.

The essay explores Bible translation in early nineteenth-century India as a comprehensive and under-appreciated site for intercultural and interreligious interactions involving Christians and Hindus in a complex context of asymmetrical colonial relations. Postcolonial theorists are interrogated for theory-driven approaches that lopsidedly rely on English-language resources without taking into account the actual Indian-language artefacts of translation projects that came into being. Using a philological approach, the essay treats the Dharmapustaka, the Sanskrit Bible translated at the Serampore Baptist Mission, as a case study in ‘transculturation’—a multidimensional process catalyzed by an English missionary, William Carey, on the edges between India and Europe.

CRISPR-based editing is a revolutionary tool for genome engineering and discovery. The pace of innovation in this young field is truly astonishing, and yet significant gaps remain in the set of capabilities offered. In particular, scalable (massively parallel and multiplex) editing is only available for a small variety of edit types, placing fundamental limits on the kinds of studies researchers can perform. Additional advancements are needed to realize the full potential of the technology.

Background SCD is a group of autosomal recessive red blood cell (RBC) disorders caused by a single point mutation in the β-globin gene, resulting in the production of hemoglobin S. Hemoglobin S polymerizes within RBCs under certain conditions, leading to the distortion of the RBC membrane and generation of dense and sickle RBCs. These pathologic RBCs contribute to microvascular occlusions in patients with SCD, which present as acute painful episodes called VOEs. Despite the majority of VOEs being managed at home, they remain the most common reason for emergency department (ED) visits and hospitalization among patients with SCD, with > 70% of ED visits and > 90% of hospital admissions for SCD being related to VOEs (Ballas et al. Am J Hematol 2005; Lanzkron et al. Am J Hematol 2010). One of the most severe complications of VOEs is acute chest syndrome, which is a leading cause of mortality among patients with VOEs (Vichinsky et al. N Engl J Med 2000; Bartolucci et al. eBioMedicine 2016). In the absence of targeted therapies for the management of VOEs in patients with SCD, treatment is currently limited to pain management, blood exchange transfusion (with the risk of complications), and other supportive care, representing a significant unmet medical need. Activation of the complement pathway has been described in patients with SCD at baseline, in acute pain crises, and in patients with delayed hemolytic transfusion reaction. Accumulating nonclinical data have suggested a multimodal role for complement dysregulation in the pathophysiology of SCD including vaso-occlusion, hemolysis, inflammation, thrombogenicity, endothelial activation, and end-organ damage (Roumenina et al. Am J Hematol 2020). Crovalimab is a novel, engineered, anti-complement C5 monoclonal antibody. In a Phase I/II study (Röth et al. Blood 2020) in patients with paroxysmal nocturnal hemoglobinuria, a complement-mediated disorder, crovalimab demonstrated rapid and sustained complement inhibition with promising efficacy and safety. Study Design and Methods CROSSWALK-a (NCT04912869) is a randomized, double-blind, placebo-controlled, Phase Ib study evaluating the safety of crovalimab for the management of acute uncomplicated VOEs in patients with SCD. Patients aged ≥ 12 years to ≤ 55 years, weighing ≥ 40 kg, and with a confirmed diagnosis of SCD homozygous hemoglobin S (HbSS) or sickle cell β 0 thalassemia (HbSβ 0) are eligible for the study (Figure). Patients must present with an acute uncomplicated VOE, requiring hospitalization and treatment with parenteral opioid analgesics. Vaccinations against Neisseria meningitidis, Hemophilus influenzae type B, and Streptococcus pneumoniae must be up to date. Eligible patients will be randomized 2:1 to receive either a single intravenous weight-based tiered dose of crovalimab or placebo. Patients in both study arms will continue to undergo pain management and receive other supportive care for their VOE and may also continue to receive ongoing concurrent SCD-directed therapies. Patients will be followed during the hospitalization until discharge and will continue to be followed post-discharge during an observational period. The maximum total study duration for an individual patient will be 12 weeks, which includes the hospitalization and observational periods. The primary objective is to evaluate the incidence and severity of adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0, incidence and severity of infusion-related reactions and hypersensitivity, and change from baseline in targeted vital signs and clinical laboratory test results. Efficacy, pharmacokinetics, pharmacodynamics, immunogenicity, and exploratory biomarker endpoints will also be evaluated. Figure 1 Figure 1. Disclosures Bartolucci: F. Hoffmann-La Roche Ltd: Consultancy; Bluebird: Consultancy, Research Funding; Emmaus: Consultancy; Hemanext: Consultancy; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; GBT: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; INNOVHEM: Other: Co-founder; Fabre Foundation: Research Funding; Addmedica: Consultancy, Other: Lecture fees, Research Funding. Ataga: Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees; Agios Pharmaceuticals: Consultancy; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees. Callaghan: Alnylum: Current equity holder in publicly-traded company; Roche/Genentech: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy; Pfizer: Consultancy; Global Blood Therapeutics: Consultancy, Speakers Bureau; uniQure: Consultancy; Spark: Consultancy; Biomarin: Consultancy; Kedrion: Consultancy; Hema Biologics: Consultancy; Forma: Consultancy; Chesei: Consultancy; Agios Pharmaceuticals: Current Employment. De Franceschi: F. Hoffmann-La Roche Ltd: Consultancy. Minniti: F. Hoffmann-La Roche: Consultancy; Bluebird Bio: Other: Endpoint adjudicator; Forma: Consultancy; GBT: Consultancy; Novo Nordisk: Consultancy; CSL Behring: Other: Endpoint adjudicator; Novartis: Consultancy; Chiesi: Consultancy. Alexandrou: F. Hoffmann-La Roche Ltd: Consultancy, Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company. Imbs: F. Hoffmann-La Roche Ltd: Consultancy; Certara Inc.: Current Employment. Fox: Parexel International: Current Employment; Genentech, Inc.: Current Employment. Patel: Genentech, Inc.: Current Employment. Sostelly: F. Hoffmann-La Roche Ltd: Current Employment.

Current research indicates that more than half of patients with traumatic spinal cord injury (tSCI) experience delays in transfer and receive surgery >24 h post-injury. The objectives of this study were to determine the geographic distribution of tSCI in Canada relative to specialized treatment facilities, to assess clinical and logistical factors at play for indirect admissions to those facilities, and to explore differences in current time to admission and simulated scenarios in an attempt to assess the potential impact of changes to triage protocols. This study included data from 876 patients with tSCI enrolled in the prospectively collected acute Rick Hansen Spinal Cord Injury Registry (RHSCIR) between January 1, 2010 and December 31, 2013 for whom there were data on the location of their injury. Patients transported directly to a RHSCIR acute facility were more likely to reach the facility within 1 h of injury, whereas those transported indirectly were more likely to arrive 7 h later. Considering the injuries occurring within 40 km of a RHSCIR acute facility (n = 323), 249 patients (77%) were directly and 74 (23%) were indirectly admitted. In the multivariate regression analysis, only older age and longer road distance remained significantly associated with being indirectly admitted to a RHSCIR facility. Compared with the current status, the median time to admission decreased by 20% (3.5 h) in the 100% direct admission scenario, and increased by 102% (8.9 h) in the 100% indirect admission scenario.

It is important for conservationists to be able to assess the risks that climate change poses to species, in order to inform decision making. Using standardised and repeatable methods, we present a national-scale assessment of the risks of range loss and opportunities for range expansion that climate change could pose for over 3000 plants and animals. Species were selected by their occurrence in England, the primary focus of the study, but climate change impacts were assessed across Great Britain, widening their geographical relevance. A basic risk assessment that compared projected future changes in potential range with recently observed changes classified 21% of species as being at high risk and 6% at medium risk of range loss under a B1 climate change scenario. A greater number of species were classified as having a medium (16%) or high (38%) opportunity to potentially expand their distribution. A more comprehensive assessment, incorporating additional ecological information, including potentially confounding and exacerbating factors (e.g. dispersal, habitat availability and other constraints), was applied to 402 species, of which 35% were at risk of range loss and 42% may expand their range extent. This study covers a temperate region with a significant proportion of species at their poleward range limit; the balance of risks and opportunities from climate change may be different elsewhere. The outcome of both risk assessments varied between taxonomic groups, with bryophytes and vascular plants containing the greatest proportion of species at risk from climate change. Upland habitats contained more species at risk than other habitats. Whilst the overall pattern was clear, confidence was generally low for individual assessments, with the exception of well-studied taxa such as birds. In response to climate change, nature conservation needs to plan for changing species distributions and an uncertain future.

Background Optimal surgical management for flexion-distraction cervical spine injuries remains controversial with current guidelines recommending anterior, posterior, and circumferential approaches. Here, we determined the incidence of and examined risk factors for clinical and radiographic failure in patients with 1-segment cervical distraction injuries having undergone anterior surgical fixation. Methods A retrospective review of 57 consecutive patients undergoing anterior fixation for subaxial flexion-distraction cervical injuries between 2008 and 2012 at our institution was performed. The primary outcome was the number of patients requiring additional surgical stabilization and/or radiographic failure. Data collected included age, gender, mechanism and level of injury, facet pattern injury, and vertebral end plate fracture. Results A total of 6 patients failed clinically and/or radiographically (11%). Four patients (7%) required additional posterior fixation. Although 2 other patients identified met radiographic failure criteria, at follow-up they had fused radiographically, were stable clinically, and no further treatment was pursued. Progressive kyphosis and translation were found to be significantly correlated with need for revision ( P P = 0.02, respectively). No differences were identified for all other clinical and radiologic factors assessed, including unilateral or bilateral facet injury, facet fracture, and end plate fracture. Conclusion This study contributes to the growing body of evidence supporting anterior fixation alone for flexion-distraction injuries. Findings suggest that current measurements of radiographic failure including segmental translation and kyphosis may predict radiographic failure and need for further surgical stabilization in some patients. Future follow-up studies assessing for independent risk factors for anterior approach failure with a validated predictive scoring model should be considered.

The British Thyroid Association recommended in new guidelines on thyroid cancer treatment [Kwak et al. (Korean J Radiol 14:110-117, 2013)] that ultrasound grading of thyroid nodules should be incorporated into MDT management. A retrospective study was carried out to determine that the impact of US grading has had on MDT decision making in practice. The design used in the study is a retrospective review of case notes. The study was carried out in the hub hospital for thyroid cancer in the North west London Cancer network. We included consecutive patients referred to the regional thyroid multidisciplinary meeting between August 2014 and May 2015 for investigation of thyroid nodules. Data were collected on patient demographics, co-morbidity, thy grading, ultrasound grading, surgery, post-operative histology, and radioactive iodine treatment details. Accuracy of cytology and ultrasound in diagnosing malignancy was correlated to definitive histology. 99 patients with thyroid nodules were included in the study. 97% of patients had at least one fine needle aspiration and 75% had ultrasound grading. Thy3f (Bethesda IV) nodules were more likely to be carcinoma if associated with a U4 grade rather than U3 (67 vs 18%, p = 0.028). Ultrasound grading has recently been introduced to the standard practice in investigation of thyroid nodules. Further assessment of the accuracy of ultrasound grading in clinical practice may allow us to risk-stratify thy3a/thy3f (Bethesda III/IV) lesions and personalise treatment.

Introduction/Background We have shown that Epigallocatechin-3-gallate (EGCG) targets the human papillomavirus (HPV)-encoded E6 and E7 oncoproteins for degradation, resulting in epithelial cell growth inhibition in in vitro models. Recent clinical trials indicated that Veregen®, a topical ointment containing 55–72 mg of EGCG, is a safe and effective treatment for vulval warts, benign lesions caused by low-risk HPV strains. Based on our findings, we undertook a phase II randomised control trial (RCT) to evaluate if Veregen® is also effective in the treatment of usual-type vulvar intraepithelial neoplasia (uVIN), a pre-malignant lesion associated with high-risk HPV infection. Methodology Eligible patients were randomised to receive either Veregen® or placebo ointment (applied 3 times daily for 16 weeks), and were followed up at 2, 4, 8, 16, 32 and 52 weeks. Outcome measures, recorded at 16 and 32 weeks, were histological (HR) and clinical (CR) response (measured by ≥30% reduction in the sum of the longest diameter of all lesions when compared to baseline) and toxicity. The primary outcome, HR, required a difference in the number of responders ≥3 in favour of Veregen® to detect a difference of 20% between groups (10% for placebo and 30% for Veregen®), as per Jung’s design with type I, II errors ≤0.15. Results 26 patients were randomised, all 13 patients who received Veregen® showed either complete (n=5) or partial (n=8) CR. In placebo group, 3 patients had complete CR, 2 had partial CR and 6 had stable disease. Patients in the Veregen® group showed significant improvement in CR as compared to the placebo group (P=0.0026). There was no evidence of difference in HR and toxicity reported in both groups. Conclusion This study indicates that Veregen® application is safe and leads to at least a partial clinical resolution of uVIN lesions, thus warranting a phase III multi-centre RCT. Disclosure The study is funded by the National Institute for Health Research via the Research for Patient Benefit programme and Medigene AG supplied Veregen® and placebo.

In 2016 there were 5250 brain cancer deaths in the UK. Standard treatment is surgical resection followed by chemo-radiotherapy. In most cases of diffuse glioma, complete tumour resection is not feasible. Many chemotherapy drugs have untested penetration through the blood brain barrier, potentially leading to sub-therapeutic concentrations in the tumour. There is need to refine current treatment strategies in relation to the understanding of tumour biology, and rapidly introduce and evaluate novel therapeutic approaches and agents through delivering rigorous clinical trials. The TESSA JOWELL BRAIN MATRIX Study will evaluate the feasibility of delivering precision medicine for brain cancer patients within the NHS. A multicentre, platform feasibility study of 1200 patients with diffuse glioma will build on the 100,000 genome project to develop and evaluate an infrastructure to collect and integrate: 1) real time comprehensive integrated molecular analysis, including whole genome sequencing and epigenetic classification; 2) serial sampling and annotation of tumours; 3) collection of matched clinical data; 4) assessment of patient quality of life; 5) centralised radiological review and response assessment as per RANO criteria. Once developed this will allow rapid introduction of therapeutic trials to specific patient groups. Secondary objectives include: understanding the association between extent of resection and molecular stratification to refine the role of surgery; optimisation and harmonisation of protocols to best collect, manage and store tissue, clinical data, and radiological images in order to provide a resource for researchers, both within and outside of the study. Improve patient recruitment by identifying and removing recruitment barriers and improve the information and consent processes for patients. Promote the development of a national network with expertise in brain cancer. Enrolment of the first patient is expected in late 2019. For further information, please contact the Brain Matrix Trial Office BrainMatrix@trials.bham.ac.uk.

A large array of species distribution model (SDM) approaches has been developed for explaining and predicting the occurrences of individual species or species assemblages. Given the wealth of existing models, it is unclear which models perform best for interpolation or extrapolation of existing data sets, particularly when one is concerned with species assemblages. We compared the predictive performance of 33 variants of 15 widely applied and recently emerged SDMs in the context of multispecies data, including both joint SDMs that model multiple species together, and stacked SDMs that model each species individually combining the predictions afterward. We offer a comprehensive evaluation of these SDM approaches by examining their performance in predicting withheld empirical validation data of different sizes representing five different taxonomic groups, and for prediction tasks related to both interpolation and extrapolation. We measure predictive performance by 12 measures of accuracy, discrimination power, calibration, and precision of predictions, for the biological levels of species occurrence, species richness, and community composition. Our results show large variation among the models in their predictive performance, especially for communities comprising many species that are rare. The results do not reveal any major trade-offs among measures of model performance; the same models performed generally well in terms of accuracy, discrimination, and calibration, and for the biological levels of individual species, species richness, and community composition. In contrast, the models that gave the most precise predictions were not well calibrated, suggesting that poorly performing models can make overconfident predictions. However, none of the models performed well for all prediction tasks. As a general strategy, we therefore propose that researchers fit a small set of models showing complementary performance, and then apply a cross-validation procedure involving separate data to establish which of these models performs best for the goal of the study., This work was funded by the Research Foundation of the University of Helsinki (A. Norberg), the Academy of Finland (CoE grant 284601 and grant 309581 to O. Ovaskainen, grant 308651 to N. Abrego, grant 1275606 to A. Lehikoinen), the Research Council of Norway (CoE grant 223257), the Jane and Aatos Erkko Foundation, and the Ministry of Science, Innovation and Universities (grant CGL2015‐68438‐P to M. B. Araújo).

Background Sorafenib is the current standard of care for patients with advanced hepatocellular carcinoma (aHCC) and has been shown to improve survival by about 3 months compared to placebo. However, survival varies widely from under three months to over two years. The aim of this study was to build a statistical model that allows personalised survival prediction following sorafenib treatment. Methods We had access to 1130 patients undergoing sorafenib treatment for aHCC as part of the control arm for two phase III randomised clinical trials (RCTs). A multivariable model was built that predicts survival based on baseline clinical features. The statistical approach permits both group-level risk stratification and individual-level survival prediction at any given time point. The model was calibrated, and its discrimination assessed through Harrell’s c-index and Royston-Sauerbrei’s R2D. Results The variables influencing overall survival were vascular invasion, age, ECOG score, AFP, albumin, creatinine, AST, extra-hepatic spread and aetiology. The model-predicted survival very similar to that observed. The Harrell’s c-indices for training and validation sets were 0.72 and 0.70, respectively indicating good prediction. Conclusions Our model (‘PROSASH’) predicts patient survival using baseline clinical features. However, it will require further validation in a routine clinical practice setting.

Objective Cancer initiation and progression has been linked to aberrant expression of the DNA methyltransferases (DNMT), the enzymes which establish and maintain DNA methylation patterns throughout the genome. In this study, we investigated if DNMT expression in vulvar squamous cell carcinomas (VSCC) was related to clinical outcome. Methods DNMT1, DNMT3A and DNMT3B expression was measured in a subset of cases drawn from a cohort of consecutive women treated for primary VSCC at the Pan Birmingham Gynaecological Cancer Centre between 2001 and 2008. Univariable and multivariable competing risk modelling was performed to identify whether DNMT expression was associated with local disease recurrence or disease morbidity. Results Over-expression of DNMT3A in the invasive component of the tumour was seen in 44% of tumours and was associated with an increased risk of local vulvar recurrence (LVR) (HR=4.51, p=0.012). This risk was found to increase further after adjustment for disease stage (HR=6.00, p=0.003) and groin node metastasis (HR=4.81, p=0.008). Over-expression of DNMT3B was associated with an increased risk of LVR (HR=5.69 p=0.03), however this ceased to be significant after adjustment for groin node metastasis. In a subset analysis, over-expression of DNMT3A was found to be significantly more common in VSCCs that stained negative for CDKN2A. Conclusions These observations are consistent with the possibility that epigenetic changes contribute to vulvar neoplasia and DNMT3A over-expression may be useful in predicting local disease recurrence.

In this study, we investigated if the presence of histologically abnormal epithelium adjacent to the primary tumour influenced the frequency, timing, and topography of local vulvar recurrences (LVR) following treatment for squamous cell carcinoma of the vulva (VSCC).The study population comprised a cohort of 201 consecutive cases with incident VSCC. LVR were categorised as local relapses (LR) if they occurred2cm from the tumour margins, and as second field tumours (SFT) when ≥2cm from these margins. Univariable and multivariable competing risk modelling was performed to identify the prognostic factors associated with local disease recurrence.The characterization of the epithelium adjacent to the invasive component was possible for 199 (99.0%) patients. Of these, 171 (85.9%) were found to have intraepithelial abnormalities found adjacent to the surgical specimen. Multivariable analyses revealed that, following adjustment, Lichen Sclerosis (LS) was associated with an increase in the incidence of LVR, LR and SFT (SHRs: 3.4, 2.7 and 4.4, respectively). Although the incidence of LR and SFT in women with LS associated VSCC was similar, the peak incidence of SFT occurred more than two years before that of LR.Women with VSCC arising in a field of LS may continue to have an increased risk of developing LR and SFT for many years after resection of their primary tumour. Our study suggests that these women should be followed up more regularly so that LVR can be detected earlier; unless a more robust surveillance programme or chemopreventative treatments become available.

Attempts to automate handwritten character recognition date back to the 1960s, but progress over the past two decades shows extremely accurate recognition of printed characters in English. The most common approaches used today apply a form of machine learning such as support vector machines (SVM) or neural networks. While highly accurate, these forms of machine learning do not attempt to apply higher-level knowledge to improve performance. This paper presents research applying SVM-trained recognizers supplemented with domain knowledge to provide top-down guidance in an attempt to improve recognition accuracy.

Citizen science is a powerful way to undertake monitoring of biodiversity, both for detecting rare events (e.g. invasive species, animal and plant health issues or presence of rare species) and assessing trends. However, in order to use citizen science effectively we need to understand better the patterns of people’s participation in projects considering variation in participation between citizen science approaches and individual variation in participation within a project. variation in participation between citizen science approaches and individual variation in participation within a project. Here, we particularly focus on the information content of the data collected through citizen science (although we recognise that citizen science has many other benefits, in addition to data collection). Firstly, we assessed participation in five projects for biodiversity monitoring in the UK, from mass participation to monitoring by volunteer experts, representing up to two thousand people per activity per year. We quantified the patterns of participation (in terms of retention of participants, spatial patterns of participation, and unevenness of contributions per participant - as in the 90:10 rule). We found that the data from mass participation projects were more strongly spatially correlated with human population density and retention of individuals was lower compared to projects targeted on those with existing interest in the subject. Secondly, we quantified the recording behaviour of recorders in a butterfly citizen science project. We developed this with four thousand users of a smartphone app designed for recording sightings of butterflies in the UK. The majority of these users were active for less than 10 days, a feature common to many citizen science projects. The users who engaged for longer produced most of the records for the project. We characterised their recording behaviour using 11 metrics that describe the variation in temporal and spatial recording behaviour as well as the data they recorded. Results showed that citizen scientists in this project fall on a continuum along 4 main axes describing their behaviour. We then used a 20-year butterfly dataset to assess the contribution of different types of recorders to the overall estimate of biodiversity trends and their precision. Overall, variation in participation, both between projects and between individuals within projects, contributes to variation in the information content (and hence the usefulness) of citizen science datasets. We show how different approaches can provide data to meet different needs for data users and how this understanding can be used to improve analyses of these data, allowing us to better design citizen science activities in the future.

[EN] Citizen science plays an increasingly important role in biodiversity research and conservation, enabling large volumes of data to be gathered across extensive spatial scales in a cost-effective manner. Open access increases the utility of such data, informing land-use decisions that may affect species persistence, enhancing transparency and encouraging proliferation of research applications. However, open access provision of recent, fine-scale spatial information on the locations of species may also prompt legitimate concerns among contributors regarding possible unintended negative conservation impacts, violations of privacy and commercial exploitation of volunteer-gathered data. Here we canvas the attitudes towards open access of contributors (104 regional co-ordinators and 510 recorders) of species occurrence records to two of the largest citizen science biodiversity recording schemes, the UK’s Butterflies for the New Millennium project and National Moth Recording Scheme. We find that while the majority of participants expressed support for open access in principle, most were more cautious in practice, preferring to limit the spatial resolution of records, particularly of threatened species, and restrict commercial reuse of data. In addition, citizen scientists’ opinions differed between UK countries, taxonomic groups and the level of involvement volunteers had in the schemes. In order to maintain successful and democratic citizen science schemes, organisers, funders and data users must understand and respect participants’ expectations and aspirations regarding open data while seeking to optimise data use for scientific and societal benefits.

517 Background: The relationship between toxicity from chemotherapy and clinical outcome in biliary tract cancer (BTC) is uncertain. Aim: This post hoc analysis evaluated differences by sex in the frequency of adverse events (AEs) and overall survival (OS) and its impact on progression-free survival (PFS)/recurrence-free survival (RFS) for BTC patients. Methods: Individual patient data were retrieved from ABC -01, -02, -03, -04, and BILCAP study. AEs were graded according to National Cancer Institute's Common Toxicity Criteria v 4.02 and odds ratios along with 95%CI and p-values derived from logistic regression were used to assess the effect of sex on the risk of AEs. Time to event outcomes were evaluated using Cox regression and plotted using Kaplan-Meier plots. All statistical tests were two-sided. Results: Overall 994 patients-data were examined: 86 in ABC-01, 324 in-02, 124 in -03, 13 in -04 and 447 in BILCAP. A total of 484 (49%) were males (M) and 510 (51%) were females (F). 770 patients were evaluable for AEs because a total of 224 patients in BILCAP study belonged to the observation group. Urinary tract infection (M, 1.6%; F, 5.5%), nausea (M, 50.7%; F, 69.9%), vomiting (M, 29.1%; F, 46.1%), alopecia (M, 11.3%; F, 27.3%), are dominant in F, hyperbilirubinaemia (M, 36.7%; F, 29.1%) and thrombocytopenia (M, 43.1%; F, 34.3%) and hiccups (M, 2.4%; F, 0.5%) are dominant in M at any grade. Vomiting (M, 3.5%; F, 7.0%) and fatigue (M, 4.0%; F, 8.5%) are higher in F than in M for grade 3-5. The median OS (M, 16.2 months (Mo); F, 17.5 Mo), PFS (M, 6.4 Mo; F, 6.5 Mo) and RFS (M, 20.8 Mo; F 19.4 Mo) were similar. Amongst the subgroup of patients with gallbladder, F achieved longer OS (M, 11.5 Mo; F 13.3 Mo, 0.73 (95%CI:0.54,0.99), p = 0.041) and RFS than M (M, 20.8 Mo; median PFS for F not reached, HR:0.52 (95%CI:0.27,1.02), p = 0.057). Conclusions: Females with BTC have tended to have more AEs, especially grade 3+. Although no difference was observed in OS, PFS, and RFS between males and females for the overall cohort of patients, females with gallbladder cancer had an improved OS and RFS compared with males. These findings suggest, in BTC, sex may play a role when designing clinical trials as well as in making treatment decisions.

Oral malignant melanoma (OMM) is the most common canine melanocytic neoplasm. Overlap between the somatic mutation profiles of canine OMM and human mucosal melanomas suggest a shared UV-independent molecular aetiology. In common with human mucosal melanomas, most canine OMM metastasise. There is no reliable means of predicting canine OMM metastasis, and systemic therapies for metastatic disease are largely palliative. Herein, we employed exon microarrays for comparative expression profiling of FFPE biopsies of 18 primary canine OMM that metastasised and 10 primary OMM that did not metastasise. Genes displaying metastasis-associated expression may be targets for anti-metastasis treatments, and biomarkers of OMM metastasis. Reduced expression of CXCL12 in the metastasising OMMs implies that the CXCR4/CXCL12 axis may be involved in OMM metastasis. Increased expression of APOBEC3A in the metastasising OMMs may indicate APOBEC3A-induced double-strand DNA breaks and pro-metastatic hypermutation. DNA double strand breakage triggers the DNA damage response network and two Fanconi anaemia DNA repair pathway members showed elevated expression in the metastasising OMMs. Cross-validation was employed to test a Linear Discriminant Analysis classifier based upon the RT-qPCR-measured expression levels of CXCL12, APOBEC3A and RPL29. Classification accuracies of 94% (metastasising OMMs) and 86% (non-metastasising OMMs) were estimated.

There has been significant progress in the treatment of metastatic melanoma, however the impact of new agents on patients with brain metastases remains poorly understood. We report outcomes using SRS for patients with melanoma brain metastases exposed to BRAF targeted agents and/or immunotherapy. METHODS Consecutive patients with metastatic melanoma and brain metastases undergoing SRS without routine whole brain radiotherapy were identified. Selection was restricted to patients having systemic therapy within the same centre. Follow-up included 3monthly MRI scans. All patients were treated using Cyberknife. The target volume was neuroradiology approved without an uncertainty margin. A review of electronic records and follow up imaging was undertaken. Survival data were summarized using Kaplan-Meier curves and compared via a logrank test. RESULTS 49 patients with 148 target metastases were identified. Median number of lesions was 2 (range 1–12), median dose 21Gy, median volume 0.31cc (range 0.01–6.71cc) and 94% had extracranial disease at 2 or more sites. Three patients did not have follow up MRI. One patient required long-term steroids, 1 had transient symptomatic swelling at 11months and 3 patients experienced bleeds (1 symptomatic- post-SRS treated lesion). 12-month local disease free survival was 71% (CI 53, 84). Distant brain progression occurred in 28 patients (57%), with a median time to progression of 8months (95% CI 5, 15). Distant brain progression was less frequent in patients with a single metastasis (p=0.03). Median overall survival (OS) was 11months (95% CI 8, 17). Median OS was 20months (95% CI 5, NR), 10months (95% CI 4, 12) and 11months (95% CI 3, NR) for patients with 1, 2–4 and ≥ 5 metastases respectively (p=0.07). CONCLUSION Beyond a single metastasis, the number of brain metastases did not correlate with OS. Patients with multiple brain metastases and active systemic disease may benefit from SRS however prospective evaluation is recommended.

Study design This is a single-center, retrospective, observational cohort study. Objective To determine whether surgery or nonoperative treatment has better clinical outcomes in neurologically intact patients with an intermediate severity thoracolumbar burst fracture. Summary of background data Optimal management, whether initial operative or nonoperative treatment, for thoracolumbar injury classification score (TLICS) 4 burst fractures remains controversial. Better insight into the treatment which affords patients a better clinical outcome could significantly affect patient care. Materials and methods This retrospective study included consecutive cases of TLICS 4 burst fracture patients from 2007 to 2013 and minimum 6-month follow-up. Potential confounders examined included age, sex, injury severity score, initial kyphotic angle, injured facets, and interspinous widening. Outcomes were determined by standardized questionnaires [Oswestry Disability Index (ODI), 12-item Short Form Physical Component Score (SF-12 PCS), and back pain Visual Analog Scale (VAS)] and analyzed using regression analysis. Results A total of 230 patients with burst fractures were identified, of which 67/230 (29%) were TLICS 4 and 47/67 (70%) had completed follow-up. No difference on univariate analysis was found between nonsurgical and surgical groups in mean ODI scores (P=0.27, t test), nor mean time to return to work (P=0.10, t test).Regarding outcomes, linear regression analysis revealed no association between having surgery and ODI (P=0.29), SF-12 PCS (P=0.59), or VAS (P=0.33). Furthermore, no difference was found between groups for employed patients working versus not working (P=0.09, the Fisher test), nor in mean time to return to work (P=0.30, Cox regression). Conclusions This is one of the largest studies examining TLICS 4 burst fracture patients, adjusting for both clinical and radiologic confounders and reporting patient outcomes with minimum 6-month follow-up. No differences were found in outcomes between patients treated either surgically or nonsurgically. Studies focusing on early postoperative differences or cost-effectiveness might help in decision making. Level of evidence Level III.

Predictable all ceramic restorations utilizing computer-aided design/computer-aided milling have been made possible by following carefully outlined directions. A combined understanding of the capabilities of software, the milling unit, ceramic properties and the bonding process allows a dentist to create indirect restorations that exhibit desirable qualities.

A cornerstone of conservation is the designation and management of protected areas (PAs): locations often under conservation management containing species of conservation concern, where some development and other detrimental influences are prevented or mitigated. However, the value of PAs for conserving biodiversity in the long term has been questioned given that species are changing their distributions in response to climatic change. There is a concern that PAs may become climatically unsuitable for those species that they were designated to protect, and may not be located appropriately to receive newly-colonizing species for which the climate is improving. In the present study, we analyze fine-scale distribution data from detailed resurveys of seven butterfly and 11 bird species in Great Britain aiming to examine any effect of PA designation in preventing extinctions and promoting colonizations. We found a positive effect of PA designation on species' persistence at trailing-edge warm range margins, although with a decreased magnitude at higher latitudes and altitudes. In addition, colonizations by range expanding species were more likely to occur on PAs even after altitude and latitude were taken into account. PAs will therefore remain an important strategy for conservation. The potential for PA management to mitigate the effects of climatic change for retracting species deserves further investigation.

BACKGROUND: Transarterial chemoembolisation (TACE) is the standard of care for patients with intermediate stage hepatocellular carcinoma, while the multikinase inhibitor sorafenib improves survival in patients with advanced disease. We aimed to determine whether TACE with sorafenib improves progression-free survival versus TACE with placebo.METHODS: We did a multicentre, randomised, placebo-controlled, phase 3 trial (TACE 2) in 20 hospitals in the UK for patients with unresectable, liver-confined hepatocellular carcinoma. Patients were eligible if they were at least aged 18 years, had Eastern Cooperative Oncology Group performance status of 1 or less, and had Child-Pugh A liver disease. Patients were randomised 1:1 by computerised minimisation algorithm to continuous oral sorafenib (400 mg twice-daily) or matching placebo combined with TACE using drug-eluting beads (DEB-TACE), which was given via the hepatic artery 2-5 weeks after randomisation and according to radiological response and patient tolerance thereafter. Patients were stratified according to randomising centre and serum α-fetoprotein concentration (FINDINGS: Between Nov 4, 2010, and Dec 7, 2015, the trial enrolled 399 patients and was terminated after a planned interim futility analysis. 86 patients failed screening and 313 remaining patients were randomly assigned: 157 to sorafenib and 156 to placebo. The median daily dose was 660 mg (IQR 389·2-800·0) sorafenib versus 800 mg (758·2-800·0) placebo, and median duration of therapy was 120·0 days (IQR 43·0-266·0) for sorafenib versus 162·0 days (70·0-323·5) for placebo. There was no evidence of difference in progression-free survival between the sorafenib group and the placebo group (hazard ratio [HR] 0·99 [95% CI 0·77-1·27], p=0·94); median progression-free survival was 238·0 days (95% CI 221·0-281·0) in the sorafenib group and 235·0 days (209·0-322·0) in the placebo group. The most common grade 3-4 adverse events were fatigue (29 [18%] of 157 patients in the sorafenib group vs 21 [13%] of 156 patients in the placebo group), abdominal pain (20 [13%] vs 12 [8%]), diarrhoea (16 [10%] vs four [3%]), gastrointestinal disorders (18 [11%] vs 12 [8%]), and hand-foot skin reaction (12 [8%] and none). At least one serious adverse event was reported in 65 (41%) of 157 patients in the sorafenib group and 50 (32%) of 156 in the placebo group, and 181 serious adverse events were reported in total, 95 (52%) in the sorafenib group and 86 (48%) in the placebo group. Three deaths occurred in each group that were attributed to DEB-TACE. Four deaths were attributed to study drug; three in the sorafenib group and one in the placebo group.INTERPRETATION: The addition of sorafenib to DEB-TACE does not improve progression-free survival in European patients with hepatocellular carcinoma. Alternative systemic therapies need to be assessed in combination with TACE to improve patient outcomes.FUNDING: Bayer PLC and BTG PLC.

Background: The Japanese ‘BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients. Methods: In this Japanese/UK collaboration, we replicated the original BALAD model on a UK cohort and then built a new model, BALAD-2, on the original raw Japanese data using variables in their continuous form. Regression analyses using flexible parametric models with fractional polynomials enabled fitting of appropriate baseline hazard functions and functional form of covariates. The resulting models were validated in the respective cohorts to measure the predictive performance. Results: The key prognostic features were confirmed to be Bilirubin and Albumin together with the serological cancer biomarkers, AFP-L3, AFP, and DCP. With appropriate recalibration, the model offered clinically relevant discrimination of prognosis in both the Japanese and UK data sets and accurately predicted patient-level survival. Conclusions: The original BALAD model has been validated in an international setting. The refined BALAD-2 model permits estimation of patient-level survival in UK and Japanese cohorts.

Following a cluster of haematology patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) septicaemia, we initiated screening for rectal carriage of CRKP and multidrug-resistant K. pneumoniae (MDRKP) in this patient group. Haematology inpatients submit a rectal swab once weekly. When plated onto chromogenic Brilliance™ UTI Agar (Oxoid), and incubated overnight with a 10 µg ertapenem disc (Oxoid), K. pneumoniae is identified and semi-automated antibiotic susceptibility testing is performed using the Vitek 2 analyser (Biomerieux). When no zone of inhibition occurs, immediate intervention through patient isolation and enhanced environmental cleaning can be instigated to control further spread while empirical antibiotic prescribing is adapted to take account of identified resistances. Over 2 years, six patients with CRKP and 20 patients with MDRKP were identified. These isolates were resistant to first-line empirical treatment choices for neutropenic sepsis and presented a clinical risk of treatment failure for sepsis post cytotoxic chemotherapy. We describe how this rectal screening methodology was developed and how the results influenced appropriate antibiotic prescribing, patient placement in single rooms and the cleaning of the ward environment to prevent person-to-person transmission of MDRKP and CRKP.

Encounters with jugular bulb abnormalities during ear surgery are a rare but recognised problem. A high riding jugular bulb is present in 10%–15% of patients and its variable position within the temporal bone can lead to problems as brisk venous haemorrhage can result if the bulb is inadvertently opened. The case of a 52-year-old woman with a central tympanic membrane perforation who underwent elective endaural myringoplasty and experienced brisk bleeding on raising the tympanomeatal flap is presented.

Computer-aided design/computer-aided milling (CAD/CAM) has grown in popularity over the last decade and is here to stay! The technology as a whole and the materials of choice are continuously evolving, allowing us to fabricate predictable restorations. Perhaps even more importantly, CAD/CAM assists us in becoming better dentists. When proper technique and attention to detail are observed in treatment planning, preparing teeth, and scanning and bonding restorations, we as dentists can predictably fabricate an esthetic and functional restoration for the patient. This chapter is written based on our experiences with Sirona’s CEREC and Planmeca’s E4D systems. The authors bring to light some basic principles that are applicable to any milled restoration as we expect more systems to emerge in the years to come.

e16151Background: The BILCAP study established capecitabine (cape) as adjuvant therapy for patients with curatively resected biliary tract cancer. An unexpected finding was the apparent lack of ben...

e16132Background: The BILCAP study outcome placed adjuvant capecitabine (cape) as the standard of care following curative surgery for biliary tract cancer (BTC). We present exploratory analyses of ...

Automated music composition typically employs genetic algorithms and/or stochastic methods using randomness in lieu of creativity. When properly guided these approaches can yield listenable music yet they lack another aspect of the music composition process: planning. Without planning, there may be no coherent structure or themes in the composed music. Planning can be employed to provide such structure by overseeing or controlling the genetic algorithm and/or stochastic methods in a hybrid architecture. In this paper, the system MAGE is presented which combines stochastic processing, genetic algorithms and planning to compose music that contains both structure and elements of randomness.

Background: Application of curative therapy for hepatocellular carcinoma is crucially dependent on underlying liver function. Using the recently described ALBI grade we examined the long-term impact of liver dysfunction on survival of early-stage hepatocellular carcinoma (HCC) patients. Methods: This cohort study comprised 2559 HCC patients from different geographic regions, all treated with curative intent. We also examined the relation between indocyanine green (ICG) clearance and ALBI score. Survival was measured from the date of treatment to the date of death or last follow-up. Results: The ALBI score correlated well with ICG clearance. Among those undergoing surgical resection, patients with ALBI grade-1 (good liver function) survived approximately twice as long as those with ALBI grade-2 (less good liver function), although more than 90% of these patients were classified as Child–Pugh (C-P) grade A. In the cohort receiving ablative therapies, there was a similar difference in survival between ALBI grade-1 and grade-2. Cox regression analysis confirmed that the ALBI score along with age, gender, aetiology and tumour factors (AFP, tumour size/number and vascular invasion) independently influenced survival in HCC patients receiving curative treatments. Conclusions: The ALBI score represents a simple approach to the assessment of liver function in patients with HCC. After potentially curative therapy, those with ALBI grade-1 survived approximately twice as long as those with ALBI grade-2. These data suggest that ALBI grade-1 patients are appropriately treated with surgical resection whereas ALBI grade-2 patients may, where the option exists, be more suitable for liver transplantation or the less invasive curative ablative therapies.

The UK Government has set targets for biodiversity conservation in England based on several indicators, including the status of protected areas [e.g. Sites of Special Scientific Interest (SSSIs)]. Specifically, the Government aims to achieve favourable condition [defined by Common Standards Monitoring (CSM)] on 95% by area of SSSIs by 2010. SSSIs are important for threatened butterflies and management to achieve favourable condition will play a key role in determining future population levels of these high-profile insects. Because only notified features of SSSIs are considered within CSM, we investigated the level of notification for three threatened butterflies. We found that these species were notified at only 15–33% of SSSIs where they occurred; though most site managers did manage for them under broader site conservation objectives. We investigated the relationship between SSSI condition status and population trend for eight butterfly species of conservation concern to assess the benefit to butterflies of sites attaining favourable condition status. The majority (80%) of population trends on SSSIs in favourable condition were positive, suggesting an overall beneficial impact of SSSI management. However, four of the eight species maintained lower populations at favourable condition SSSIs than at sites in one of the unfavourable condition categories. We suggest that current condition assessment based chiefly on notified vegetation communities lacks the sensitivity to identify the complex habitat conditions for these (mosaic) species. As butterflies are good indictors for a wide range of invertebrates, many species requiring fine-scale habitat heterogeneity may be at risk from the Government’s target.