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Introduction The pre-hospital environment provides significant challenges to clinicians who wish to rapidly administer warmed blood products and fluids to patients with haemorrhagic shock. Large-bore circulatory access is required with the use of devices that will successfully warm cold blood with minimal impact on flow rates. Until now, no information has been available that defines UK Helicopter Emergency Medical Services’ (HEMS) use of circulatory access and fluid warming devices, nor the recent adoption of pre-hospital blood product transfusion. Methods A survey was sent to all 22 UK HEMS asking which circulatory access devices crews have available, whether blood products are being transfused and if fluid warming devices are used as part of their resuscitations. Results All services responded. All UK HEMS use peripheral intravenous cannulae and intraosseous access. In addition, seven use central venous catheters and three use large-bore peripheral access (the Arrow Rapid Infusion Catheter®). Three services use landmark technique alone to gain central venous access, whereas four use a combination of landmark and ultrasound-guided techniques. Different sites for central venous access are used: subclavian (seven services), internal jugular (four) and femoral (four). Fourteen services carry pre-hospital blood products of which six transfuse packed red blood cells; four transfuse packed red blood cells and fresh frozen plasma; four transfuse packed red blood cells and lyophilised plasma. Eight services carry no pre-hospital blood products. Seventeen HEMS use fluid warmers; 13 use the Belmont® buddy lite™ and four use the QinFlow Warrior. Conclusion The use of a variety of policies and range of equipment has evolved across UK HEMS, demonstrating a lack of consensus on best practice. This is the first study to record a complete picture of current UK HEMS practice with regard to the use of circulatory access devices, fluid warmers and blood product administration.

Immune checkpoint inhibitors (ICIs) are active in metastatic urothelial carcinoma (MUC). They have joined chemotherapy (CT) as a standard of care. Here, we investigate the activity of CT after progression on ICIs. Two cohorts of sequential patients with MUC were described ( n =28). Cohort A received first-line ICIs followed by CT after progression. Cohort B received CT after failure of first-line platinum-based CT followed by ICIs. Response rate (RR) to CT was assessed using Response Evaluation Criteria in Solid Tumors (RECIST v1.1) by a designated radiologist. Best RR for cohort A was 64%. Two patients experienced clinical progression and died before the first radiographic assessment. RR for cohort B was 21%, which was significantly lower than that for cohort A. Progression of disease occurred in 43% of cohort B patients by the end of CT. These data suggest a lack of cross resistance between CT and ICIs in MUC. Therefore, the sequencing of these drugs is likely to be important to maximise outcomes. This is particularly true after first-line ICIs as subsequent CT has significant activity. Patient summary In this report, we studied the effect of chemotherapy in metastatic bladder cancer, which relapsed after immune checkpoint inhibitors. We found that the activity of chemotherapy was maintained despite previous exposure to immune therapy. This underlines the importance of sequencing these agents to maximise outcomes.

A saltern associated with salt production was excavated at Pyde Drove, near Woolavington. The large assemblage of briquetage recovered has allowed for some novel interpretations of the function of the different component types within the hearth structures. The saltern comprised a mound of waste material adjacent to 12 brine-settling tank pits and two salt water channels. A further settling tank was revealed beneath the mound. The pottery indicates that activity on the site dates to the later Romano-British period.

This article describes several approaches to assessing student understanding using written explanations that students generate as part of a multiple-document inquiry activity on a scientific topic (global warming). The current work attempts to capture the causal structure of student explanations as a way to detect the quality of the students’ mental models and understanding of the topic by combining approaches from Cognitive Science and Artificial Intelligence, and applying them to Education. First, several attributes of the explanations are explored by hand coding and leveraging existing technologies (LSA and Coh-Metrix). Then, we describe an approach for inferring the quality of the explanations using a novel, two-phase machine-learning approach for detecting causal relations and the causal chains that are present within student essays. The results demonstrate the benefits of using a machine-learning approach for detecting content, but also highlight the promise of hybrid methods that combine ML, LSA and Coh-Metrix approaches for detecting student understanding. Opportunities to use automated approaches as part of Intelligent Tutoring Systems that provide feedback toward improving student explanations and understanding are discussed.

IntroductionGiven the need for more bladder cancer research and the recently observed advantages of introducing the trials within cohort (TwiCs) design, the set-up of the Graham Roberts Study (Roberts Study) will provide valuable infrastructure to answer a wide variety of research questions of a clinical, mechanistic, as well as supportive care nature in the area of bladder cancer.MethodsUsing the TwiCs design, we will recruit patients aged 18 or older who are willing and able to provide signed informed consent and have a diagnosis of new or recurrent bladder cancer into this prospective cohort study. All patients must have a basic understanding of the English language. The following questionnaires will be collected at baseline and every 12 months subsequently: Functional Assessment of Chronic Illness Therapy for Bladder Cancer, the Functional Assessment of Chronic Illness Therapy-Fatigue, the Patient Heath Questionnaire-9, the standardised instrument for a generic health status (EQ-5D-5L), a Short Questionnaire to Assess Health-Enhancing Physical Activity and the Hertfordshire Short Questionnaire to Assess Diet Quality.Ethics and disseminationDue to the nature of this study, we obtained full ethical clearance from the London—Fulham Research Ethics Committee (17/LO1975). All participants must provide full informed consent before recruitment onto the study. The results of this study will be published in peer-reviewed journals and data collected as part of the study will be made available to potential collaborators on an application basis.

Consensus in Bladder Cancer Research Priorities Between Patients and Healthcare Professionals Using a Four-stage Modified Delphi Method

Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) is a life-threatening complication of T-lymphocyte deplete allogeneic hematopoietic stem cell transplantation (allo-HSCT). For patients with PTLD refractory to Rituximab, donor lymphocyte infusion (DLI) is established as a successful option for salvage therapy. However, although in vivo lymphocyte expansion has been correlated with good clinical outcome following DLI, the specificity and functional characteristics of EBV-specific T-cell responses remain poorly characterized. Here we describe two patients with Rituximab-refractory PTLD complicating T-cell deplete allo-HSCT, both of whom were successfully rescued with 1 × 106/Kg unselected stem cell donor-derived DLI. Prospective analyses revealed that complete clinical and radiological responses were associated with in vivo expansion of T and NK cells. Furthermore, EBV MHC tetramer, and interferon gamma analyses revealed a marked increase in EBV-specific T-cell frequency from 4 weeks after DLI. Reactivity was demonstrated against a range of EBV latent and lytic antigens, including those detected in tumor biopsy material. The immunodominant EBV-specific T cell response expanding in vivo following infusion matched the dominant response present in the DLI preparations prior to administration. Furthermore, differences in the repertoire of subdominant antigen-specific T-cells were also detected, suggesting that antigen-encounter in vivo can shape the immune response. These results demonstrate the value of prospectively studying in vivo T-cell responses, by facilitating the identification of important specificities required for clinical efficacy. Applying this approach on a larger scale promises to yield data which may be essential for the optimization of future adoptive immunotherapeutic strategies for PTLD.

Purpose To determine the impact on clinical management of patients with high-risk (HR) prostate cancer at diagnosis and patients with biochemical recurrence (BCR) using a new kit form of 68Ga-prostate-specific membrane antigen (PSMA), namely tris(hydroxypyridinone) (THP)-PSMA, with positron emission tomography-computed tomography (PET-CT). Methods One hundred eighteen consecutive patients (50 HR, 68 BCR) had management plans documented at a multidisciplinary meeting before 68Ga-THP-PSMA PET-CT. Patients underwent PET-CT scans 60-min post-injection of 68Ga-THP-PSMA (mean 159 ± 21.2 MBq). Post-scan management plans, Gleason score, prostate-specific antigen (PSA) and PSA doubling time (PSAdt) were recorded. Results HR group: 12/50 (24%) patients had management changed (9 inter-modality, 3 intra-modality). Patients with PSA < 20 μg/L had more frequent management changes (9/26, 34.6%) compared with PSA > 20 μg/L (3/24, 12.5%). Gleason scores > 8 were associated with detection of more nodal (4/16, 25% vs 5/31, 16.1%) and bone (2/16, 12.5% vs 2/31, 6.5%) metastases. BCR group: Clinical management changed in 23/68 (34%) patients (17 inter-modality, 6 intra-modality). Forty out of 68 (59%) scans were positive. Positivity rate increased with PSA level (PSA < 0.5 μg/L, 0%; PSA 0.5–1.0 μg/L, 35%; PSA 1.0–5.0 μg/L, 69%; PSA 5.0–10.0 μg/L, 91%), PSAdt of < 6 months (56% vs 45.7%) and Gleason score > 8 (78.9% vs 51.2%). Conclusions 68Ga-THP-PSMA PET-CT influences clinical management in significant numbers of patient with HR prostate cancer pre-radical treatment and is associated with PSA. Management change also occurs in patients with BCR and is associated with PSA and Gleason score, despite lower scan positivity rates at low PSA levels < 0.5 μg/L.

TPS266 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinizing hormone releasing hormone analogue (LHRHA), is standard of care for men with very high-risk localized prostate cancer (PC), or with very high- risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high-risk features. Darolutamide is a structurally distinct oral androgen receptor antagonist with low blood-brain-barrier penetration, a demonstrated favorable safety profile and low potential for drug-drug interactions. Our aim is to determine the efficacy of adding darolutamide to ADT and RT in the setting of either primary definitive therapy, or adjuvant therapy for very high-risk PC. Methods: This study is a randomized (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localized PC; or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: RP; use of adjuvant docetaxel; pelvic nodal involvement. 1100 participants will be randomized to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with up to 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival (ICECaP-validated), with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment. Clinical trial information: NCT04136353.

Radiotherapy remains a key modality in the palliation of advanced malignancy managing both local primary tumour effects such as pain and bleeding as well as the sequelae of metastatic disease. Its role continues to evolve in line with advances in radiation technology, which have facilitated dose escalation and reduced toxicity. Injudicious use of such advancements has the potential to magnify the cost of delivering palliative radiotherapy without achieving significant gains in terms of outcomes, and therefore well-designed trials to assess the clinical efficacy are essential. From a policy perspective a key concern remains the heterogeneity in dose fractionation schedules currently utilised internationally which lack a strong evidence base and may be influenced by reimbursement policy that incentivises longer, more complex and less cost-effective schedules. International consensus is required on study end-points in palliative radiotherapy research to enable comparison between case series and facilitate randomised controlled trial design. Patient reported outcome measures should be developed that capture the value of radiation treatment for different indications both in achieving symptom control but also improving quality of life. The timing and appropriate use of radiation therapy are generally guided by the clinical assessment of the radiation oncologist, once a referral has been made. An analysis of outcomes from national-level epidemiological studies has the potential to guide appropriate utilisation and identify those patients most likely to derive benefit from radiotherapy in different tumour types. Lastly education and training remain at the heart of reducing inequalities in access to radiotherapy for patients who would benefit. This includes both radiation oncologists for whom many training schemes do not prioritise palliative care and the wider multidisciplinary team who are involved in the management of cancer patients at all stages.

Recent educational standards stress that students should learn how to read and understand scientific explanations and create explanations of their own. But these skills are difficult for teachers to evaluate, so they often assess them at a shallow level or avoid giving such assignments. Previous approaches for automatically evaluating explanatory and other types of structured essays have relied on the use of shallow features or bag-of-words methods. These methods might allow for a reasonable holistic assessment of an essay, but they fail to identify which concepts students included and which causal connections they made. In this paper, we investigate which natural language processing methods are most successful at locating conceptual information in student explanations and the causal connections between them. We found that a combination of a recurrent neural network for identifying concepts along with a novel causal relation parser produced very good accuracy in two different scientific domains, significantly improving on the prior state-of-the-art.

TPS385 Background: Radiation therapy (RT), plus androgen deprivation therapy (ADT) with a luteinising hormone releasing hormone analogue (LHRHA) for at least one year, is standard of care for men with very high-risk localised prostate cancer (PC), or with very high-risk features and persistent PSA after radical prostatectomy (RP). Despite this, incurable distant metastases develop within 5 years in 15% of men with very high risk features. Darolutamide is an androgen receptor antagonist with favourable tolerability. Our aim is to determine the efficacy of adding darolutamide to ADT and RT given in the setting of either primary definitive therapy (RP or RT), or adjuvant therapy for very high-risk PC. Methods: This study is a randomised (1:1) phase III placebo-controlled, double-blind trial for men planned for RT who have very high-risk localised PC, or very high-risk features with PSA persistence or rise within one year following RP. The trial will be stratified by: use of adjuvant docetaxel; pelvic nodal involvement; RP. 1100 participants will be randomised to darolutamide 600 mg or placebo twice daily for 96 weeks. Participants will receive LHRHA for 96 weeks, plus RT starting week 8-24 from randomisation. Participants are allowed nonsteroidal antiandrogen (up to 90 days) in addition to LHRHA up until randomisation. Early treatment with 6 cycles of docetaxel completed at least 4 weeks prior to RT is permitted. The primary endpoint is metastasis-free survival, with secondary endpoints overall survival, PC-specific survival, PSA-progression free survival, time to subsequent hormonal therapy, time to castration-resistance, frequency and severity of adverse events, health related quality of life, fear of recurrence. Tertiary endpoints include incremental cost-effectiveness, and identification of prognostic and/or predictive biomarkers of treatment response, safety and resistance to study treatment. Clinical trial information: NCT04136353.

Total en bloc spondylectomy (TES) is a surgical technique that is indicated for primary malignant bone tumours, aggressive benign tumours and infrequently solitary metastatic lesions. Primary bone tumours in the axial skeleton are rare. It’s estimated they comprise 11% of all primary bone tumours and only 4% of all tumours found in the spine (1,2). Conversely metastatic spine disease is a significant health burden.

Objectives/Scope From the very early days of oil and gas exploration, appraisal and development drilling, samples have been collected at the rig by mud logging personnel to conduct a preliminary geological analysis of the rock being drilled. This collection typically involves a sample collection recipient, board or bucket to collect a sample of rock over the desired interval. The sample is then sieved and cleaned in the appropriate way depending on the type of drilling fluid being used. As penetration rates have increased in some instances to more than 400 ft. / hr. the sample resolution has deteriorated exponentially. From an ergonomics perspective, the highest frequency to which a person onsite can collect a sample is once every 20 minutes. At 300 ft. / hr. this translates to 100 ft. of drilled rock. A new device has been developed and deployed which automates this manual process and thus ensures faster and more accurate collection of geological samples of the drilled rock interval. Sample resolutions of 5ft rock intervals have been attained at 400 ft./ hr. This technology has provided an important technological breakthrough and enables reduction of personnel at the rig site with a subsequent reduction in cost and HSE risk, particularly in areas of H2S. It further has provided for the potential integration with Measurement while drilling personnel. For both conventional and unconventional play development, this has provided oil and gas operators with an important and cost and risk reducing modus operandi compared to conventional drilling and evaluation techniques. The tool was deployed for an operator in West Texas where both manually collected traditional mudlog samples and automatically collected samples were taken. The samples were analyzed and compared for rock content. In addition, comparisons were made between point sampling with the automated system versus samples collected over a defined interval manually. Results of these comparisons will be presented. Results, Observations, Conclusions A new method of automated drill cuttings sample collection has been successfully deployed. The new method provides a step change improvement in accuracy and resolution for sampling the rock record during drilling. Novel/Additive Information Additional data of the rock record provides potential insights to optimize wellbore placement and provide increased geo-mechanical data to optimize completions.

Radiotherapy is widely used as a curative treatment for pelvic malignancies. The location of these organs leads to unavoidable exposure of the bladder, urethra, and distal ureters to radiation and may cause subsequent development of radiation cystitis, fistulae, strictures, and secondary malignancy. As cancer survival improves, an ever-increasing number of patients is living with the long-term complications of radiotherapy. Symptoms are not only debilitating for the patient but also pose a treatment challenge to the urologist. This review provides a comprehensive overview of the pathophysiology, clinical presentation, and current management strategies for the urologic complications following pelvic radiotherapy.

Background: Although comorbidities are identified in routine oncology practice, intervention plans for the coexisting needs of older people receiving chemotherapy are rarely made. This study evaluates the impact of geriatrician-delivered comprehensive geriatric assessment (CGA) interventions on chemotherapy toxicity and tolerance for older people with cancer.Methods: Comparative study of two cohorts of older patients (aged 70+ years) undergoing chemotherapy in a London Hospital. The observational control group (N=70, October 2010–July 2012) received standard oncology care. The intervention group (N=65, September 2011–February 2013) underwent risk stratification using a patient-completed screening questionnaire and high-risk patients received CGA. Impact of CGA interventions on chemotherapy tolerance outcomes and grade 3+ toxicity rate were evaluated. Outcomes were adjusted for age, comorbidity, metastatic disease and initial dose reductions.Results: Intervention participants undergoing CGA received mean of 6.2±2.6 (range 0–15) CGA intervention plans each. They were more likely to complete cancer treatment as planned (odds ratio (OR) 4.14 (95% CI: 1.50–11.42), P=0.006) and fewer required treatment modifications (OR 0.34 (95% CI: 0.16–0.73), P=0.006). Overall grade 3+ toxicity rate was 43.8% in the intervention group and 52.9% in the control (P=0.292).Conclusions: Geriatrician-led CGA interventions were associated with improved chemotherapy tolerance. Standard oncology care should shift towards modifying coexisting conditions to optimise chemotherapy outcomes for older people.Keywords: comprehensive geriatric assessment; elderly; geriatric oncology; chemotherapy tolerance; toxicity; interventions

There is an increasing emphasis, especially in STEM areas, on students’ abilities to create explanatory descriptions. Holistic, overall evaluations of explanations can be performed relatively easily with shallow language processing by humans or computers. However, this provides little information about an essential element of explanation quality: the structure of the explanation, i.e., how it connects causes to effects. The difficulty of providing feedback on explanation structure can lead teachers to either avoid giving this type of assignment or to provide only shallow feedback on them. Using machine learning techniques, we have developed successful computational models for analyzing explanatory essays. A major cost of developing such models is the time and effort required for human annotation of the essays. As part of a large project studying students’ reading processes, we have collected a large number of explanatory essays and thoroughly annotated them. Then we used the annotated essays to train our machine learning models. In this paper, we focus on how to get the best payoff from the expensive annotation process within such an educational context and we evaluate a method called Active Learning.

A 47-year-old man presented with a 9-year history of a hypoalert hypoactive behaviour syndrome, caused by the deep brain swelling variant of spontaneous intracranial hypotension. Along with apathy with retained cognition, he had stable ataxia, impaired upgaze and episodes of central apnoea. MRI brain showed a sagging brainstem, pointed ventricles and reduced angle between the vein of Galen and the straight sinus, but no meningeal enhancement or subdural collections. A dopamine transporter scan showed preganglionic dopamine receptor deficiency; a fluorodeoxy glucose positron emission tomography scan showed bilateral hypothalamic hypometabolism. This variant of spontaneous intracranial hypotension may alter deep brain functioning within the basal ganglia and thalamus, causing the hypoactive-hypoalert behaviour phenotype.

Objective To examine prostate-specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide. Methods We retrospectively identified 30 consecutive patients with metastatic prostate cancer who were treated with enzalutamide after docetaxel. Post-discontinuation PSA results were available for all patients and were determined at 2-weekly intervals until starting further anticancer systemic therapy. PSA withdrawal response was defined as a PSA decline by >= 50% from the last on-treatment PSA, with a confirmed decrease >= 3 weeks later. Patient characteristics were evaluated in relation to the AAWS using univariate logistic regression analysis. Results The median (range) patient age was 70.5 (56-86) years and the median (range) follow-up was 9.0 (0.5-16) months. The most common metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients (70%) had previously received abiraterone and 12 patients (40%) had also received cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68 (1.12-21.39) months. PSA levels after enzalutamide withdrawal were monitored for a median (range) time of 35 (10-120) days. Only one patient (3.3%) had a confirmed PSA response >= 50% after enzalutamide discontinuation. One patient (3.3%) had a confirmed PSA response of between 30 and 50% and another patient (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall survival was 15.5 months (95% CI 8.1-24.7). None of the factors analysed in the univariate analysis were significant predictors of PSA decline after enzalutamide discontinuation. Conclusions This retrospective study provides the first evidence that enzalutamide may have an AAWS in a minority of patients with metastatic castration-resistant prostate cancer. Further studies are needed to confirm the existence of an enzalutamide AAWS and to assess its relevance in prostate cancer management.

Schematic maps are an important component of assistance for navigating transport networks worldwide. By showing routes as simple straight lines, they reduce the cognitive load of journey planning, and by revealing the underlying structure of networks, they make their key features easier to identify and learn. However, although there are many suggestions for optimizing schematic maps so as to maximize these benefits, to date these have not been directly supported by published usability studies or psychological theory. In this paper, we suggest that there are circumstances in which conventional schematic maps fail to yield benefits, and we compare journey planning using the current official RATP Paris Metro map with an all-curves design which replaces straight lines and corners with gentle curves. Three separate usability studies with slightly different methodologies showed that the journey planning time for the all-curves map was better than the RATP version, with effect sizes ranging from 0.48 to 1.12. Subjective usability ratings were derived from questionnaires, and user preferences, but neither were correlated with objective usability measures. We conclude that (1) in terms of designing schematics, there is no evidence to suggest that any rule-set can be claimed to be a gold-standard, and it is important to match the design rules to the properties of the network, (2) in some circumstances, radical departures from traditional ideas can yield usability benefits, and (3) map usability appears to be distinct from map engagement, although the latter is undoubtedly important in encouraging people fully to make use of navigation aides.

Prostate cancer is the commonest solid cancer in men, with approximately 42,000 new cases per year in the United Kingdom [1]. This section details the evidence-based management of prostate cancer at all stages.

North American unconventional well completion design has evolved dramatically since 2013 in an effort to keep pace with the productivity gains realized in horizontal drilling. Several trends have emerged during the current industry downturn. Among these trends are a focus on core acreage with higher yield potential, the use of longer laterals, a movement towards higher proppant loading (pounds per linear foot), an increased reliance on plug and perf techniques, and decreased stage length and perforation cluster spacing (increased perf density). As a result associated improvements in well initial production (IP) rates and estimated ultimate recoveries (EUR's) have been highlighted in oil & gas operator's quarterly shareholder's reports during 2015 and early 2016. Unconventional multi-stage completion designs have also quickly evolved along a path paralleling these trends. Horizontal well IP rates and EUR's have also been enhanced through the adoption of integrated completion designs. Recently introduced geo-engineered completions rely on cross-functional expertise and software to integrate petrophysical, geomechanical, drilling, and production data into a completion design. In cases where geo-engineered designs were used, wells showed improvements in EUR's over those associated with increased lateral lengths, proppant loading and stage counts. In one recent case using a geo-engineered design it was demonstrated that fewer stages and clusters achieved higher production than offset wells while injecting less proppant and fluid; thus achieving lower completion cost. The use of engineered workflows in tight or unconventional reservoirs is not new. Multiple case histories have been published in recent literature illustrating the use of stress variability/contrast or mechanical specific energy (MSE) to generate brittleness or other fraccability indices to group stages with similar rock characteristics. In contrast to engineered designs, newer geo-engineered designs integrate multiple inputs (attributes) to determine basin and formation-specific weighted algorithms that correlate to stage and cluster production contribution improvement. The geo-engineered approach has proven repeatable and can be accomplished even when key wireline or LWD data is not available. This paper will document how geo-engineered completion designs evolved from engineered workflows. Multiple inputs (e.g. production, wireline/LWD/mud logs, core analyses, and big data from national and state data bases) can be combined to determine stage length and perforation cluster positioning. Case studies will demonstrate that geo-engineered horizontal completion designs deliver superior well production results when compared to geometric, high-intensity plug & perf designs.

INTRODUCTION Bilateral balloon occlusion has been employed as a prophylactic measure in cases of placenta accretism prior to caesarean section with the aim of reducing blood loss and its associated morbidity/mortality. There is however no clear consensus on its efficacy in the current literature. The objective of this study was to assess the efficacy of bilateral balloon occlusion of the common iliac arteries (CIA) in reducing intra-operative morbidity in cases of placenta accretism. METHODS The databases of the pathology department and radiology interventional suite were reviewed over a nine year period. Fifty-two cases of confirmed placental accretism who underwent caesarean section with or without hysterectomy were identified and divided into two groups. Twenty-five cases had temporary occlusion of the common iliac arteries (CIA) during delivery and these were considered the study group. The reminder 27 cases did not have temporary occlusion of the CIA and were considered the control group. The two groups were compared based on gravidity, age group, post-operative haemoglobin, drop in haemoglobin, estimated blood loss (EBL), transfusion requirement and the histopathological sub-types of placenta accretism. RESULTS There was no statistically difference between the study and the control groups regarding EBL, post-operative haemoglobin drop, transfusion requirement or in the placenta accretism histopathological subtype. Two cases in the study group had acute thromboembolic complications. Both groups had a single patient requiring a massive intra-operative transfusion. CONCLUSION Our study was not able to detect a significant difference in blood loss or blood product requirement between patients who underwent CIA balloon in the setting of caesarean section for placenta accreta. This remains a challenging scenario requiring a multidisciplinary approach.

The present study explored different approaches for automatically scoring student essays that were written on the basis of multiple texts. Specifically, these approaches were developed to classify whether or not important elements of the texts were present in the essays. The first was a simple pattern-matching approach called "multi-word" that allowed for flexible matching of words and phrases in the sentences. The second technique was latent semantic analysis (LSA), which was used to compare student sentences to original source sentences using its high-dimensional vector-based representation. Finally, the third was a machine-learning technique, support vector machines, which learned a classification scheme from the corpus. The results of the study suggested that the LSA-based system was superior for detecting the presence of explicit content from the texts, but the multi-word pattern-matching approach was better for detecting inferences outside or across texts. These results suggest that the best approach for analyzing essays of this nature should draw upon multiple natural language processing approaches.

Respiratory motion can vary dramatically between the planning stage and the different fractions of radiotherapy treatment. Motion predictions used when constructing the radiotherapy plan may be unsuitable for later fractions of treatment. This paper presents a methodology for constructing patient-specific respiratory motion models and uses these models to evaluate and analyse the inter-fraction variations in the respiratory motion. The internal respiratory motion is determined from the deformable registration of Cine CT data and related to a respiratory surrogate signal derived from 3D skin surface data. Three different models for relating the internal motion to the surrogate signal have been investigated in this work. Data were acquired from six lung cancer patients. Two full datasets were acquired for each patient, one before the course of radiotherapy treatment and one at the end (approximately 6 weeks later). Separate models were built for each dataset. All models could accurately predict the respiratory motion in the same dataset, but had large errors when predicting the motion in the other dataset. Analysis of the inter-fraction variations revealed that most variations were spatially varying base-line shifts, but changes to the anatomy and the motion trajectories were also observed.

Introduction Tenascin-C (TNC) is a large extracellular matrix glycoprotein that shows prominent stromal expression in many solid tumours. The profile of isoforms expressed differs between cancers and normal breast, with the two additional domains AD1 and AD2 considered to be tumour associated. The aim of the present study was to investigate expression of AD1 and AD2 in normal, benign and malignant breast tissue to determine their relationship with tumour characteristics and to perform in vitro functional assays to investigate the role of AD1 in tumour cell invasion and growth. Methods Expression of AD1 and AD2 was related to hypoxanthine phosphoribosyltransferase 1 as a housekeeping gene in breast tissue using quantitative RT-PCR, and the results were related to clinicopathological features of the tumours. Constructs overexpressing an AD1-containing isoform (TNC-14/AD1/16) were transiently transfected into breast carcinoma cell lines (MCF-7, T-47 D, ZR-75-1, MDA-MB-231 and GI-101) to assess the effect in vitro on invasion and growth. Statistical analysis was performed using a nonparametric Mann-Whitney test for comparison of clinicopathological features with levels of TNC expression and using Jonckheere-Terpstra trend analysis for association of expression with tumour grade. Results Quantitative RT-PCR detected AD1 and AD2 mRNA expression in 34.9% and 23.1% of 134 invasive breast carcinomas, respectively. AD1 mRNA was localised by in situ hybridisation to tumour epithelial cells, and more predominantly to myoepithelium around associated normal breast ducts. Although not tumour specific, AD1 and AD2 expression was significantly more frequent in carcinomas in younger women (age ≤40 years; P < 0.001) and AD1 expression was also associated with oestrogen receptor-negative and grade 3 tumours (P < 0.05). AD1 was found to be incorporated into a tumour-specific isoform, not detected in normal tissues. Overexpression of the TNC-14/AD1/16 isoform significantly enhanced tumour cell invasion (P < 0.01) and growth (P < 0.01) over base levels. Conclusions Together these data suggest a highly significant association between AD-containing TNC isoforms and breast cancers in younger women (age ≤40 years), which may have important functional significance in vivo.

e17022Background: Docetaxel is now a standard of care for the treatment of newly diagnosed castrate-sensitive metastatic prostate cancer. However, the PREVAIL, AFFIRM and COU-AA studies demonstrati...

TPS156 Background: Adjuvant ADT with an LHRH analog (LHRHA) given before, during and after radiotherapy (RT) is standard of care for high risk localised prostate cancer (PC). Enzalutamide improves overall survival (OS) in castration-resistant, metastatic prostate cancer. We hypothesized that the addition of enzalutamide to adjuvant ADT and RT will improve outcomes. The aim is to determine the effects of enzalutamide versus a conventional non-steroidal anti-androgen (NSAA) as part of neoadjuvant and adjuvant ADT in men undergoing RT for high risk, localized PC. Methods: DESIGN: Open label, randomised, phase 3 trial including ANZ, USA, UK, Ireland and Europe. ENDPOINTS: OS (primary), cause-specific survival, PSA progression free survival (PFS), clinical PFS, time to subsequent hormonal therapy, time to castration-resistant disease (PCWG2 criteria), metastasis free survival (MFS), adverse events and health-related quality of life (HRQOL). CORRELATIVE OBJECTIVES: identification of prognostic/predictive biomarkers from archival tumour tissue and serial blood samples. SAMPLE SIZE: 800 participants with a minimum follow-up of 5.5 yrs is designed to give 80% power to detect 33% reduction in the hazard of death assuming 5-year survival rate of 76% amongst controls. TREATMENT: Enzalutamide 160mg daily for 24 months versus conventional NSAA for 6 months. All participants receive LHRHA for 24 months, and RT starting about week 16 delivered as 78Gy in 39#, or 46Gy in 23# plus brachytherapy (nodal RT optional for N0, mandatory for N1). ASSESSMENTS: Baseline, then every 8 weeks until year 2, then 3-4 monthly until year 5, 6-monthly until year 7, then annually. Imaging with CT/MRI and bone scan at baseline, PSA progression, then 6 monthly until re-initiation of ADT, when PCWG2 criteria for CRPC are met and then 3 monthly until evidence of metastases. 623 participants recruited from 61 sites as of 16 October 2017. ENZARAD is an investigator-initiated cooperative group trial led by ANZUP Cancer Trials Group with funds and product from Astellas. Clinical trial information: NCT02446444.

Educational standards put a renewed focus on strengthening students' abilities to construct scientific explanations and engage in scientific arguments. Evaluating student explanatory writing is extremely time-intensive, so we are developing techniques to automatically analyze the causal structure in student essays so that effective feedback may be provided. These techniques rely on a significant training corpus of annotated essays. Because one of our long-term goals is to make it easier to establish this approach in new subject domains, we are keenly interested in the question of how much training data is enough to support this. This paper describes our analysis of that question, and looks at one mechanism for reducing that data requirement which uses student scores on a related multiple choice test.

Analysis of the chicken genome has shown that the chicken has a different repertoire of chemokines and chemokine receptors to those of mammals and other species. In this study, we report the sequencing and analysis of a bacterial artificial chromosome containing the entire chicken MIP family CC chemokine cluster. The gene duplication and divergence events that have taken place in mammals do not appear to have occurred as extensively in the avian lineage, as chickens possess fewer MIP family chemokine genes than humans or mice. We previously proposed that the four chicken MIP family members be named chicken (ch) CCLi1-4, according to their position on chicken chromosome 19, until such time as further analysis could determine if any of them were direct orthologues of mammalian MIP family members. Our analysis herein, combined with that of others, suggests that chCCLi4 is the orthologue of mammalian CCL5, and that chCCLi3 (K203) may be an orthologue of human CCL16. The other two chemokines do not have obvious orthologues, and thus we propose that they should still be called chCCLi1 and chCCLi2, until their biological function is further characterised. A similar pattern applies to the MIP family chemokine receptors, with only three receptor genes present at the relevant locus in the chicken genome, compared to four in man and mouse (CCR1, CCR2, CCR3 and CCR5). Of the three chicken receptor genes, only two look likely to be receptors for the MIP family chemokines, the third grouping with human, mouse and chicken CCR8 in phylogenetic analysis. The two chicken MIP CC receptors (CCRs) are not direct orthologues of the mammalian MIP CCRs.

Purpose To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumor doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.

Background Melanotic neuroectodermal tumor of infancy (MNTI) is exceptionally rare and occurs predominantly in the head and neck (92.8 % cases). The patient reported here is only the eighth case of MNTI presenting in an extremity, and the first reported in the fibula. Case presentation A 2-month-old female presented with a mass arising in the fibula. Exhaustive genomic, transcriptomic, epigenetic and pathological characterization was performed on the excised primary tumor and a derived cell line. Whole-exome analysis of genomic DNA from both the tumor and blood indicated no somatic, non-synonymous coding mutations within the tumor, but a heterozygous, unique germline, loss of function mutation in CDKN2A (p16INK4A, D74A). SNP-array CGH on DNA samples revealed the tumor to be euploid, with no detectable gene copy number variants. Multiple chromosomal translocations were identified by RNA-Seq, and fusion genes included RPLP1-C19MC, potentially deregulating the C19MC cluster, an imprinted locus containing microRNA genes reactivated by gene fusion in embryonal tumors with multilayered rosettes. Since the presumed cell of origin of MNTI is from the neural crest, we also compared gene expression with a dataset from human neural crest cells and identified 185 genes with significantly different expression. Consistent with the melanotic phenotype of the tumor, elevated expression of tyrosinase was observed. Other highly expressed genes encoded muscle proteins and modulators of the extracellular matrix. A derived MNTI cell line was sensitive to inhibitors of lysine demethylase, but not to compounds targeting other epigenetic regulators. Conclusions In the absence of somatic copy number variations or mutations, the fully transformed phenotype of the MNTI may have arisen in infancy because of the combined effects of a germline CDKN2A mutation, tumor promoting somatic fusion genes and epigenetic deregulation. Very little is known about the etiology of MNTI and this report advances knowledge of these rare tumors by providing the first comprehensive genomic, transcriptomic and epigenetic characterization of a case. Electronic supplementary material The online version of this article (doi:10.1186/s12885-016-2669-3) contains supplementary material, which is available to authorized users.

Prior to 2004, the uro-oncology community viewed the management of advanced or metastatic prostate cancer with an air of resigned nihilism. Now, the range of therapeutic options available is the subject of ongoing debate and the British Uro-oncology Group (BUG) is collating oncologist opinions on the future management of castration-sensitive disease. Historically, treatment for metastatic prostate cancer was limited to androgen deprivation therapy (ADT) with the aims of delaying disease progression and palliating symptoms. Patients invariably progressed, developing castration-resistant disease with limited effective therapeutic options. This article is protected by copyright. All rights reserved.

Background Incidence and mortality from traumatic intra-cranial haemorrhage (ICH) is increased in patients on warfarin [1]. Prothrombin Complex Concentrates (PCC) rapidly reverse warfarin anti-coagulation and have been shown to reduce haematoma expansion and mortality in warfarinised patients sustaining ICH [2]. We aimed to determine the feasibility of pre-hospital use of PCCs by physicians and their clinical effectiveness in warfarinised patients sustaining traumatic ICH.