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The study aimed to describe the understanding of evolution of 10-11 year olds at primary schools in England and investigated whether their understanding can be improved when they are exposed to instruction. Evolution is a unifying concept in biology and although existing literature indicated that evolution is poorly understood by many adults, including teachers and children at secondary school, it was recently introduced in the English National Curriculum for primary school. Research is needed to clarify to what extent it is possible to improve primary school children’s understanding of this complex concept. There is very limited research with primary school children, so it is unclear whether the inclusion of evolution provides primary school teachers with a realistic aim or whether challenges will arise from its inclusion in the National Curriculum. In order to analyse the impact of instruction on the understanding of evolution, a teaching intervention was designed using the principles of Cognitive Acceleration through Science Education (CASE). CASE aims to promote cognitive development as well as the understanding of science concepts; in this study, the CASE framework was implemented in the study of evolution. The intervention focussed on six concepts hypothesised to be core elements of the concept of evolution; variation, inheritance, adaptation, domestication, speciation and extinction. The impact of the intervention was evaluated using an experimental design, which included a pre- and post-test and the random assignment of pupils to the intervention or the control groups. At pre- and post-test, pupils completed as assessment of cognitive development as well as an assessment that covered the six core elements involved in understanding evolution. The participants were 114 Year 6 (10-11 years old) children from two primary schools in England. They were randomly allocated to one of three groups: evolution intervention, an active control group who participated in an intervention about electricity or an unseen control group. The electricity intervention was also designed according to the principles of CASE. The unseen control group received no instruction. It was predicted that: (1) the evolution group would perform better than the two other groups in the assessment of understanding of evolution; (2) both the evolution and the electricity group would perform better than the unseen control group in an assessment of cognitive development. Analyses of covariance showed that the evolution group performed significantly better than the unseen and electricity control groups in their understanding of evolution as measured by the assessment of the six core concepts. The quality of written justifications and the frequency of technical vocabulary used correctly in the assessment significantly increased for the evolution group when compared to the other two groups. There was no difference between the groups on the measure of cognitive development. This study makes several methodological and empirical contributions to knowledge: a fully piloted assessment tool appropriate for children aged 10-11, a detailed study of children’s understanding of evolution and a rigorously evaluated teaching intervention designed for this age group which has educational implications for curriculum design, resources and teacher training. In addition the study makes theoretical contributions with regards to the conceptual understanding of evolution of 10-11 year olds by detailing which concepts are harder to understand than others.

As part of the wider RES4BUILD framework, a report led by partners ARUP assessed the possible impacts in terms of operational greenhouse gas reduction of the solution proposed and tested within the project. Detailed research of the European Building Market, using existing statistical data, supports the selection of 4 typologies in 4 different climates. The research presents a clear outline of the stock, indicating a majority of area in the residential sector and a high density of property in the North & West regions. Renovation and innovative solutions are required as the majority of building stock uses fossil fuels like gas or oil for the major share in energy use: space heating. In this scenario analysis, there is a full reduction in fossil fuel consumption as the RES4BUILD system is electricity based. However, the EU28 model only represents an estimated 86% of the building stock and therefore assuming fossil fuel use in all other buildings it is an 86% reduction in fossil-fuel consumption. Results from the detailed comparison analysis indicate implementation of the RES4BUILD system on the building typologies of SFH, MFRB, Commercial office, and Public-School across the EU would result in an estimated 75% reduction in GWP CO2e emissions compared to a typical gas boiler and AC system. The GWP % CO2e savings will improve as the electricity grid continues to decarbonise. This is shown in table 1. It is noted that this a high level ‘best case’ scenario with full implementation of the RES4BUILD system. In reality there is likely to be several barriers and market constraints to the RES4BUILD system that will limit implementation. This will be investigated further in Task 7.2., This project has received funding from the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 814865 (RES4BUILD). This output reflects only the author's view. The European Climate, Infrastructure and Environment Executive Agency (CINEA) and the European Commission cannot be held responsible for any use that may be made of the information contained therein. While this publication has been prepared with care, the authors and their employers provide no warranty with regards to the content and shall not be liable for any direct, incidental or consequential damages that may result from the use of the information or the data contained therein. Reproduction is authorised providing the material is unabridged and the source is acknowledged.

Background Cystic Fibrosis (CF) is a genetic condition affecting approximately 200 children and young people in Northern Ireland. A diagnosis of CF is life-changing for patients and their families. At diagnosis they are provided with a wealth of educational information. This can often be overwhelming at what is already a particularly challenging time. Consequently the CF team were keen to develop a resource which would enable patients and their families to access reliable educational information in their own time which would be of benefit both at the time of diagnosis and as they grew older. Methods We decided to create an app which could be downloaded and accessed free of charge. During the design process we consulted with medical professionals, CF specialist nurses, dieticians, physiotherapists, pharmacists, clinical psychologists and social workers in addition to patients and their families. Results We created an app containing information about the local adult and paediatric CF services and providing links to useful online resources in addition to material on physiotherapy, dietetics, medications, common infections, evolving research and the transition process. The app was made available to patients in 2018. To date it has been accessed over 3,200 times. Verbal feedback has been very positive. It costs approximately £75 per year to publish online and is updated regularly by members of the multidisciplinary team. Conclusions The app has already proved a useful resource for patients and their families. We are keen to continue to develop this resource by formally evaluating and adjusting the content accordingly., Background and Aims Type 1 diabetes requires significant self-management. Teenagers have motivation but are also vulnerable. The Flash Glucose monitoring system is a device that measures interstitial glucose level by scanning the sensor placed upon the arm. Does flash glucose monitoring improve the HBA1c and overall satisfaction in 12-16 year old patients with type 1 diabetes with suboptimal levels? Methods Flash glucose monitoring was made available to all patients with type 1 diabetes who fulfilled set criteria and after completing a training session. We included 12-16 year olds with hba1c 69 mmol/mol (8.5%) and above. Demographic details were recorded. We monitored their HbA1c at 3 and 6 months from starting flash glucose monitoring. We also asked them 2 questions - Do you feel the flash glucose monitoring system has made it easier for you to manage your diabetes on a day to day basis - Do you think it will improve your overall HbA1c level? Results 24 patients aged 12-16 years had Hba1c above 69mmol/mol 8 were eliminated either due to recent diagnosis of type 1 diabetes (3) or refusal to use Libre (5) therefore N=16. Median: HbA1c before starting Libre= 78mmol/mol (mean=85), at 3 months 86 mmol/mol ( mean=85) and 6 months 73mmol/mol ( mean 73) p=0.016 At 3 months all felt Libre made it easier to manage day to day sugar levels Conclusion There was a significant fall in Hba1c (P=0.016) 6 months after using Flash Glucose monitoring. Most felt it improved overall satisfaction, Background and Aims In the SHSCT diabetes team, our goal is to empower our young people and encourage selfmanagement of their diabetes. A key component of this is to understand the expectations of young people attending our clinics, and therefore provide patient centred consultations. Our aim was to identify each patient’s goals and specific areas for discussion when attending clinic. Methods We distributed questionnaires, the in form of a ‘mind bubble’, to young people over 12 years attending paediatric diabetes clinics in the Southern Trust over a two month period. A ‘mind bubble’ is a simplified visual questionnaire designed to be user-friendly and engage with young people. Young people were asked ‘What would you like to discuss today at your diabetes clinic?’ and their responses were then addressed at that attendance. Results We received 32 completed ‘mind bubbles’. The most common response was for advice on hyper- and hypoglycaemia (44%). 7 responses (22%) were regarding practical advice on holidays and exercise, 6 responses (19%) for specific questions regarding insulin pumps and infusion sets, and 3 (9%) regarding the use of associated computer programmes. 3 responses (9%) asked for education on ketones. Conclusions The ‘mind bubble’ provides a practical way for young people to inform the diabetes team of their expectations for each clinic visit. The wide variety of responses highlights the challenges of engaging with young people with complex, life long conditions, and the need for patient centred care to enable our young people grow in confidence., BACKGROUND Nursing handovers represent the transfer of professional responsibility for patient care between team members. Patient safety depends on clear and accurate handovers. Staff surveys in 2014 identified dissatisfaction with previous handover practice. Verbal handovers occurred away from the patient bedside, without use of standardised communication tools. An opportunity to improve nursing handovers was identified. AIMS To achieve 90% compliance of Bedside Nursing Handovers. To improve staff, patient and parent satisfaction. To create a culture of handover practice which prioritises patient safety METHODS A literature search was performed to identify best practice. Staff feedback exercises and “brainstorming” allowed evidence based interventions to be tailored to address specific shortcomings. Plan-Do-Study-Act cycles focused on: Face-to-face education/staff training SBAR communication tool implementation Introduction of written handover proformas Improving start and end times (minimising interruptions) Improving accuracy of patient information transfer Utilisation of the Patient Safety Scan (safety checklist) -Regular audits monitored compliance. Results were displayed on a noticeboard for staff to identify areas for improvement and celebrate success. RESULTS Bedside handovers have increased from 0% to 100%. Parents and patients listen to handovers and have an opportunity to contribute. All handovers utilise SBAR communication and patient safety checks (namebands, PEWS charts, fluid balances, airway equipment and medications). Staff and parental feedback has demonstrated increased satisfaction and confidence with this safer, holistic, patient-centred handover. CONCLUSIONS Nursing bedside handovers have become routine practice in Maynard- Sinclair Ward and staff, patient and parental feedback continues to be extremely positive., Background & Aims In the paediatric patient, weight is required to calculate drug dosages and fluid prescriptions. In some instances, an actual weight measurement is not possible or practical and an estimate must be made. This study aimed to compare the accuracy of weight estimation using the current versus previous APLS formulae in Northern Irish children. Methods The actual weight and age of patients was collected from patient records from children attending the RBHSC Paediatric Emergency Department in April 2016 (n=523). The estimated weight using current and previous APLS formulae was calculated for each subject and compared to actual weight using the mean residual sum of squares (RSS). A sub-analysis of age groups was conducted (1-11 months; 1-5 years; 6-12 years; 13+ years). Results The Mean RSS across all age groups was 46.75 for the current formulae versus 103.23 for the previous formula. The comparative Mean RSS (current:previous formulae) for specified age groups was as follows: (1-11 months 1.65:4.88 n=82; 1-5 years 10.29:10.29 n=231; 6-12 years 77.85:181.12 n=185 ; 13+ years 301.40:708.13 n=25). Conclusion The current APLS formula is overall more accurate than the previous APLS formula at estimating weight in children and across almost all age groups (note: the formulae for 1-5 year olds were equivalent). Weight estimates are less accurate in older children with both calculation methods., Background & Aims Most studies explore children and young people’s (CYP’s) experience of healthcare without consulting CYP directly. The aim of this study is to explore “what is known about children and young people’s experiences of receiving healthcare from their present perspective?” Methods Scoping review methodology was used to address the research question through a phenomenological lens of direct quotation. Basic numerical analysis and qualitative content analysis was completed. Results 3095 CYP, aged 0-18 years, participated in the 89 studies included in this literature review at an international level. Studies describing CYPHCEs through direct quotations have increased from 2005. Most studies used semi-structured participatory interviews. CYPHCEs are complex and unique to that individual. Twelve themes emerged. Communication and autonomy were the most common themes. CYP are asking for better communication at an understandable level. Conclusions CYP have an increasingly active voice in qualitative healthcare research at an international level. A lack of patient-specific communication, which acknowledges the patient’s ability to understand, has a negative impact on CYPHCEs. CYP’s participation in their own care affects their experience, however, the level of participation each seeks is varies., Background and aims Fit Families for the Future launched in May 2019 and is presently Northern Ireland’s only multidisciplinary service for children (4-16 years) with BMI > 98th centile. Over 12 months we aim to support 48 children to achieve a healthier BMI. Methods Children are referred by paediatricians, GPs and school nurses. Each family is invited to clinic for holistic assessment by a paediatrician, physiotherapist, associate psychologist and dietician. Outcome measures include BMI, 6-minute walk test, grip strength, blood pressure testing, dietary history and quality-of-life measures. Parents are encouraged to have their own weight/BMI checked. An individualised family plan is coproduced. Treatments include a series of educational evening classes and/or oneto-one input from dietetics/physiotherapy/health coaching. Outcome measures will be reassessed at 3, 6 and 12 months. Results Currently 30 children have attended Fit Families assessment clinics. 29 are in the treatment phase. 1 child discharged as 12kg. One child’s BMI increased, and another’s remained static. Family and staff feedback have been overwhelmingly positive. Conclusions In response to feedback we have extended our evening class programme to 6-weeks, introduced text reminders for appointments and strengthened our outreach programme with community organisations including Parkrun and local councils. We are excited to recruit more families, see more results from the programme and develop a viable business case for this gap in paediatric services., Background and Aims Medication administration errors (MAE) are a common problem. To address this problem it is important to understand the how and why MAEs occur. The study aims to investigate; ° Type and characteristics of MAE; ° Underlying factors that led to these errors. Methods A mixed methods study of clinical incident reports related to MAE was undertaken. MAEs involving children 0-16 years, in paediatric medical and surgical wards in Northern Ireland (NI) between 2011- 2015 were included. The characteristics and types of MAE were quantified, then MAE descriptions were thematically analysed t determine the underlying contributing factors which led to error. Results In total 369 incident reports of MAEs (including 391 drugs) were analysed. The most common: MAE type was omitted and delayed (n=103; 28%). The most common drug class was antimicrobials (n=93; 24). MAE characteristics include; children 5 years and under (n=178; 48%); insignificant harm (n=257; 70%); Contributing themes were related to management and organisational processes; features of the team, environment, task, and patient; and unsafe acts of staff. Defences were also found but commonly occurred after MAEs reached the patient. Conclusion This research has found there are multiple types, characteristics and contributing factors associated with MAE. The findings should be used to target specific error types, drug classes and contributing factors to prevent potential MAEs in future practice., BACKGROUND White coats to lanyards, did we solve the infection control risk problem? Lanyards serve as a quick method of identifying the position of staff. However, with infection control becoming a prominent clinical priority, we are washing our hands but are we washing our lanyards? By exploring hygiene practices with regards to lanyards we can assess whether there is a need for change in the responsibility we take for what hangs around our neck. AIM To assess the lanyard hygiene practices of healthcare professionals within a district general hospital. METHOD A mixed-method survey of healthcare staff with dichotomous, nominal and free-text responses which were analysed numerically and thematically. RESULTS This questionnaire provided information on potential gaps relating to appropriate lanyard infection control measures. Common themes demonstrated that the majority of lanyards were not washed nor replaced regularly, despite being worn continuously throughout the day, including travel to and from work. Gaps in staff adherence and understanding of adequate lanyard hygiene were evident. CONCLUSION The survey reiterated the need for clear information and guidance with regards to lanyard hygiene practices. The data collected raises awareness of the current discontinuity in attention and supply of adequate information in order to empower staff to take responsibility for their neck-suspended lanyard. The implementation of a lanyard hygiene protocol and consideration of future movement towards rubberised lanyards are practical measures that could improve upon infection control standards within hospitals., Background & Aims Some people choose not to vaccinate their children resulting at least in part to a rise in the incidence of vaccine preventable disease such as measles globally. Interactions between Health Care Professionals (HCP) and parents help to alleviate vaccination concerns. What is the prevalence and cause of vaccine hesitancy or refusal in mothers attending antenatal clinics in a District General Hospital? Can targeted intervention strategies such as group educational sessions improve confidence in vaccine safety? Can educational sessions delivered to HCP about ‘vaccine safety & having conversations with vaccine hesitant families’ improve their confidence to undertake these discussions? Methods 147 consecutive mothers attending antenatal clinics filled questionnaires. Data including prevalence and spectrum of vaccine hesitancy with causation was obtained and analysed. Bespoke information sharing sessions on vaccine safety and having conversations with vaccine hesitant parents were delivered by trained HCP to families and HCP respectively. Feedback was analysed Results Majority of mothers had no concerns about vaccinating their baby (86%)with commonest concerns being ‘side effects like fever and allergic response’ followed by ‘link between MMR and autism’ 2 ‘Vaccine safety’ sessions for families significantly increased their confidence in vaccine safety (p=0.0004) 4 ‘Vaccine safety & having conversation’ sessions attended by multidisciplinary HCP significantly increased their confidence in the above area (p=0.001) Conclusions Majority of families are confident about the safety and efficiency of vaccines. Education and vaccine safety sessions targeted towards families and HCP both increase the confidence in vaccine safety., Fragile X Syndrome (FXS) is often described as the most common cause of intellectual disability (ID) in males. Anecdotally, we have noted a low diagnostic yield from FXS testing. FXS is typically caused by a triplet repeat expansion (>200 CGGs) in FMR1. FXS more commonly affects males, however it is estimated that one third of females are symptomatic. Classical features of FXS include ID, autism, behavioural disturbance and dysmorphism. Smaller expansions in FMR1 (pre-mutations) are associated with Fragile XAssociated Tremor/Ataxia Syndrome (FXTAS) and Premature Ovarian Insufficiency (POI). We retrospectively reviewed the results of FMR1 assays undertaken at the NIRGC between 24/05/12 – 08/07/19. In total, 521 FMR1 assays were performed for a variety of indications (FXS, FXTAS, POI and carrier status). Thirteen full mutations (>200 repeats) and 34 pre-mutations (59-200 repeats) were identified. All but two of those patients with a full mutation had a known family history of FXS. Of those with a full mutation, five were male and eight were female. Five of the females had symptoms of FXS. Our findings suggest a low diagnostic yield from FMR1 assays, particularly in the absence of a family history. It is also noteworthy that an equal number symptomatic females and males were diagnosed. This may be a reflection of the small sample size and/or ascertainment bias. We propose that FXS testing should not be undertaken as a first line investigation in children with ID, and only sought if there is a high degree of clinical suspicion, or a known family history.

Background: Neurally adjusted ventilatory assist (NAVA) is an emerging mode of respiratory support that uses the electrical activity of the diaphragm (Edi) to provide synchronised inspiratory pressure support, proportional to an infant’s changing inspiratory effort. Data on Edi reference values for neonates are limited. The objective of this study was to establish reference Edi values for preterm and term neonates. Methods: This was a prospective observational study of newborn infants breathing spontaneously in room air. The Edi signal was monitored by a specialised intragastric feeding tube with embedded electrodes positioned at the level of the diaphragm. Edi minimums and peaks were recorded continuously for four hours. Results: 24 newborn infants (16 preterm [

This document discusses a fatal crash from March 23, 2018 involving a Tesla Model X using the partially automated 'Autopilot' function. It provides a critique of the NTSB's report and examines the findings from a human factors perspective to contribute towards an enhanced understanding of the circumstances related to this crash. It concludes with areas for open discussion, recommendations for future investigation and five findings of worthwhile of further consideration.\ud \ud • We question whether 'driver distraction' is an appropriate classification for a "probable cause" of the crash.\ud \ud • We disagree that "familiarization with the vehicle" was not a contributing factor related to this crash.\ud \ud • We question the conclusion that driver qualification was not a contributing factor related to this crash.\ud \ud • We highlight the need for regulatory bodies to ensure effective driver state monitoring and urge for regulation on minimum requirements for driver state monitoring in partially automated vehicles.\ud \ud • We highlight the importance of human-machine interface design in a human-machine shared system and urge for regulation on minimum requirements of such systems within partially automated vehicles.\ud \ud And in doing so we highlight the importance for a human factors perspective of such events.

To determine the effects of lower (=0.3) versus higher (=0.6) initial fractional inspired oxygen (FiO 2 ) for resuscitation on death and/or neurodevelopmental impairment (NDI) in infants

Ireland, France, and Prussia : a selection from the speeches and writings of John Mitchel with an introduction by J. de L. Smyth. Introduction contains biographical information about John Mitchel. Extracts from John Mitchel's speeches and writings reprinted variously from The Irish Citizen, and The Nation. Extract from writing of Patrick James Smyth, p.[5].Printed: Dublin, Talbot Press.

Background Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18–88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82–1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74–0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78–1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information ISRCTN 81261306; EudraCT Number: 2006-005505-64

Due to a miscommunication during the production of this article, the members of the ACST-2 Collaborative Group were not properly indexed in PubMed. This has now been corrected online. We apologize for any confusion or inconvenience that this oversight might have caused.

Excitement about the dramatic increase in potential successful anticancer medicines in recent years is hampered by the high costs involved as well as the length of time traditional pathways take for regulatory approval. The translation of experimental clinical data into real-world evidence is also problematic. While the randomised controlled trial remains the gold standard for assessing efficacy and safety, there is increasing interest in the use of observational data to enable more rapid, informed and widespread availability and access to important anticancer medicines. Taking real-world evidence into account in regulatory and health technology assessment in a thoughtful and balanced fashion will enrich and justify sound decision-making. © 2018. This is the authors’ accepted and refereed manuscript to the article. Locked until 18.7.2019 due to copyright restrictions. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/

Excitement about the dramatic increase in potential successful anticancer medicines in recent years is hampered by the high costs involved as well as the length of time traditional pathways take for regulatory approval. The translation of experimental clinical data into real-world evidence is also problematic. While the randomised controlled trial remains the gold standard for assessing efficacy and safety, there is increasing interest in the use of observational data to enable more rapid, informed and widespread availability and access to important anticancer medicines. Taking real-world evidence into account in regulatory and health technology assessment in a thoughtful and balanced fashion will enrich and justify sound decision-making.

Aim: The diagnosis of tongue-tie (or ankyloglossia) has increased more than 10-fold in some countries. Whether this is a global phenomenon or related to cultural and professional differences is uncertain. Methods: An online survey in English, Japanese, Chinese and Spanish was disseminated between May and November 2016 via 27 international professional bodies to >30 clinical professions chosen a priori to represent occupations involved in the management of neonatal ankyloglossia. Results: A total of 1721 responses came from nursing (51%), medical (40%), dental (6%) and allied health (4%) clinicians. Nurses (40%) and allied health (34%) professionals were more likely than doctors (8%) to consider ankyloglossia as important for lactation problems, as were western (83%) compared to Asian (52%) clinicians. Referrals to clinicians for ankyloglossia management originated mainly from parents (38%). Interprofessional referrals were not clearly defined. Frenectomies were most likely to be performed by surgeons (65%) and dentists (35%), who were also less likely to be involved in lactation support. Clinicians performing frenectomies were more likely to consider analgesia as important compared to those not performing frenectomies. Conclusion: The diagnosis and treatment of ankyloglossia vary considerably around the world and between professions. Efforts to standardise management are required.

Background The benefits of endovascular repair of ruptured abdominal aortic aneurysm remain controversial, without any strong evidence about advantages in specific subgroups. Methods An individual‐patient data meta‐analysis of three recent randomized trials of endovascular versus open repair of abdominal aortic aneurysm was conducted according to a prespecified analysis plan, reporting on results to 90 days after the index event. Results The trials included a total of 836 patients. The mortality rate across the three trials was 31·3 per cent for patients randomized to endovascular repair/strategy and 34·0 per cent for those randomized to open repair at 30 days (pooled odds ratio 0·88, 95 per cent c.i. 0·66 to 1·18), and 34·3 and 38·0 per cent respectively at 90 days (pooled odds ratio 0·85, 0·64 to 1·13). There was no evidence of significant heterogeneity in the odds ratios between trials. Mean(s.d.) aneurysm diameter was 8·2(1·9) cm and the overall in‐hospital mortality rate was 34·8 per cent. There was no significant effect modification with age or Hardman index, but there was indication of an early benefit from an endovascular strategy for women. Discharge from the primary hospital was faster after endovascular repair (hazard ratio 1·24, 95 per cent c.i. 1·04 to 1·47). For open repair, 30‐day mortality diminished with increasing aneurysm neck length (adjusted odds ratio 0·69 (95 per cent c.i. 0·53 to 0·89) per 15 mm), but aortic diameter was not associated with mortality for either type of repair. Conclusion Survival to 90 days following an endovascular or open repair strategy is similar for all patients and for the restricted population anatomically suitable for endovascular repair. Women may benefit more from an endovascular strategy than men and patients are, on average, discharged sooner after endovascular repair., Strong evidence of equivalence

Due to a miscommunication during the production of this article, the members of the ACST-2 Collaborative Group were not properly indexed in PubMed. This has now been corrected online. We apologize for any confusion or inconvenience that this oversight might have caused.

A 10.5-year-old cat was received with sudden anorexia and dyspnea. Ultrasonographic examination of the thoracic cavity revealed that the heart was compressed by a mass on its right aspect. At necropsy, a peritoneo-pericardial diaphragmatic hernia was found, and a portion of the liver and omentum were found within the pericardial sac. Histopathology of the herniated liver revealed the presence of a neoplastic mass characterized by numerous adipocytes, myeloid and erythroid progenitor cells including megakaryocytes and bone spicules (myelolipoma). Peritoneo-pericardial diaphragmatic herniation of the liver is usually an asymptomatic congenital defect in cats. It is considered as an incidental finding and it is frequently associated with hepatic myelolipoma in feline species. &nbsp, Se presenta un gato de 10,5 años de edad con anorexia repentina y disnea. Al examen ultrasonográfico de tórax se detectó una masa que comprimía el corazón en el lado derecho. A la necropsia se observó una hernia diafragmática peritoneo pericárdica, misma que contenía segmentos de omento e hígado atrapados dentro del saco pericárdico. Al análisis microscópico, se observó un tejido de neoformación en el segmento de hígado herniado, el cual presentaba un gran número de adipocitos, megacariocitos y células progenitoras mieloides y eritroides, además de pequeños fragmentos óseos. La hernia diafragmática peritoneo pericárdica con atrapamiento hepático es un defecto congénito generalmente asintomático en gatos. Su hallazgo suele ser incidental, y se ha observado que generalmente se asocia al mielolipoma hepático en felinos. &nbsp

Docetaxel (Taxotere), a new semisynthetic taxoid, is a potentially important chemotherapeutic agent for the treatment of cancer. Forty patients with bidimensionally measurable advanced adenocarcinoma of the colon were treated with docetaxel 100 mg m-2 every 3 weeks as a 1 h infusion without routine premedication. Thirty-nine patients were eligible: 23 males and 16 females. Median age was 60 years (range 41-75) and WHO performance status 1 (0-2). Prior adjuvant chemotherapy was performed in four patients and prior radiotherapy in nine patients. Bidimensionally measurable disease sites included: Liver in 26 patients, lymph nodes and abdominal/peritoneal masses in 13, lung/mediastinal masses in ten and subcutaneous nodes in four. The median number of cycles given was 2 (range 1-15). Thirty-three patients were evaluable for response. One patient (3%) achieved a complete response and two (6%) (95% confidence limits 0-14%) a partial response. Side-effects were similar to those observed in other studies. Docetaxel, given at this dosage and schedule, has minimal activity in the treatment of colorectal carcinoma. © Macmillan Press Ltd., 1994. 70 2 376 379

Thirty-seven eligible patients, median age 59 years (range 37-72) and median performance status 1 (0-2), with advanced, untreated, measurable gastric carcinoma were given docetaxel, 100 mg m-2 i.v. over 60 min without premedication, once every 3 weeks. Metastatic sites included the liver in 12 patients and retroperitoneal lymph nodes in 16. Eight of the 33 evaluable patients (24%) achieved a partial remission for a median of 7.5 months (3-11+). An additional 11 patients had stabilisation of disease. The patients received a median of four cycles of docetaxel (range 1-8) for a total of 156 courses. Dose reduction was necessary in 30 cycles; 14 cycles were delayed a mean of 3 days. Haematological toxicity consisted mainly of non-cumulative neutropenia, with a median nadir count of 0.35 x 10(9) l-1 (0.04-1.64) and eight episodes (5%) of leucopenic fever; non-haematological toxicities included alopecia, mild nausea and vomiting and allergic manifestations such as skin rash and pruritus. There were no drug-related deaths. Our data indicate that docetaxel is an active agent in advanced gastric cancer; further clinical investigations seem warranted.

Contains fulltext : 88112.pdf (Publisher’s version ) (Closed access) BACKGROUND: Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. METHODS: The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. FINDINGS: The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006). Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). INTERPRETATION: Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery. FUNDING: Medical Research Council, the Stroke Association, Sanofi-Synthelabo, European Union.

Fourth International Airborne Remote Sensing Conference and Exhibition/21st Canadian Symposium on Remote Sensing, June 21-24, 1999, Ottawa, Ontario

In the years since Giant’s release as a major Hollywood film, its complex portrait of the western hero and twentieth-century racism has been overshadowed by the legend of James Dean as one of America’s pre-eminent cultural icons. But ironically, Edna Ferber’s construction of the poor white ranch-hand, Jett Rink, and Dean’s performance are crucial in understanding Ferber and director George Stevens’ confrontation with the darker side of America’s frontier myths and Giant’s enduring racial legacy. This article examines Ferber and Stevens’ critique of postwar masculinity, the ideology of the western, and Texas racism within the context of Jett Rink’s transgressive racial hybridity.

In a multicentre randomized trial of the EORTC-ECSG, we have treated 38 chemotherapy naive patients with advanced non-small-cell lung cancer (NSCLC) with EO9, a novel bioreductive alkylating indoloquinone. The drug was given at two different dose schedules by a single bolus i.v. injection: arm A 12 mg/m2 weekly and arm B 22 mg/m2 every three weeks. All together 185 courses were administered (145 in arm A and 40 in arm B). The major toxicity was reversible proteinuria more frequently occurring in the three-weekly schedule (arm A 34.5% vs. arm B 62.5%). Creatinine elevation, fluid retention and pericardial or pleural effusion were also recorded in a limited number of patients. Other common toxicities more frequent in the three-weekly administration were asthenia (21% vs. 35% of cycles), nausea (15% vs. 27.5% of cycles) and Vomiting (5% vs. 17.5% of cycles). Toxicities were mainly of grade I and II. No responses have been observed. Five patients (26%) on arm A and eight (53%) on arm B experienced stable disease. These doses and schedules of EO9 do not yield activity in NSCLC. 7 5 529 531

Article describing how grid computing works and what it can be used for, including potential commercial applications (1 page).

International audience

The United Kingdom Coordinating Committee on Cancer Research represents the major organizations funding cancer research in the United Kingdom. The deliberations of a working party convened by the committee to evaluate recently expressed concerns that the changes in the NHS threaten research, especially clinical trials to evaluate new treatments, are reported. A survey of contributors to trials coordinated by the committee showed that half are now experiencing difficulties in continuing to participate in clinical trials. The two major problems identified were lack of time and of staff, especially for NHS staff in non-teaching hospitals. Recent changes in junior doctors' hours and proposed reductions in the length of time for training will exacerbate this. It is possible to identify the direct and indirect excess costs of conducting research in the NHS, but currently the mechanism does not exist to designate funds specifically for this purpose. Consultation with the regional directors of research and development confirmed that the service increment for teaching and research is not the solution for this. Proposals are made to secure future clinical research in the NHS, including finance, indemnity, the licensing of new drugs, the greater use of nurse counsellors, and the value of cancer registries.

Thirty-seven eligible patients, median age 59 years (range 37-72) and median performance status 1 (0-2), with advanced, untreated, measurable gastric carcinoma were given docetaxel, 100 mg m(-2) i.v. over 60 min without premedication, once every 3 weeks. Metastatic sites included the liver in 12 patients and retroperitoneal lymph nodes in 16. Eight of the 33 evaluable patients (24%) achieved a partial remission for a median of 7.5 months (3-11 +). An additional 11 patients had stabilisation of disease. The patients received a median of four cycles of docetaxel (range 1-8) for a total of 156 courses. Dose reduction was necessary in 30 cycles; 14 cycles were delayed a mean of 3 days. Haematological toxicity consisted mainly of non-cumulative neutropenia, with a median nadir count of 0.35 x 10(9) I-1 (0.04-1.64) and eight episodes (5%) of leucopenic fever; non-haematological toxicities included alopecia, mild nausea and vomiting and allergic manifestations such as skin rash and pruritus. There were no drug-related deaths. Our data indicate that docetaxel is an active agent in advanced gastric cancer; further clinical investigations seem warranted.

The alphavirus Semliki Forest (SFV) is an enveloped virus with a positive single-stranded RNA genome. The genome is complexed with 240 copies of a capsid protein into a nucleocapsid structure. In the membrane the virus carries an equal number of copies of a membrane protein heterodimer. The latter oligomers are grouped into clusters of three. These structures form the spikes of the virus and carry its entry functions, that is receptor binding and membrane fusion activity. The membrane protein heterodimer is synthesized as a p62E1 precursor protein which upon transport to the cell surface is cleaved into the mature E2E1 form. Recent studies have given much new information on the assembly and entry mechanism of this simple RNA virus. Much of this work has been possible through the construction of a complete cDNA clone of the SFV genome which can be used for in vitro transcription of infectious RNA. One important finding has been to show that a spike deletion variant and a capsid protein deletion variant are budding-negative when expressed separately but can easily complement each other when transfected into the same cell. This shows clearly that enveloped viruses use different budding strategies: one which depends on a nucleocapsid-spike interaction as exemplified by SFV and another one which is based on a direct core-lipid bilayer interaction as shown before to be the case with retroviruses. Another important finding concerns the activation process of the presumed fusion protein of SFV, the E1 subunit. In the original p62E1 heterodimer E1 is completely inactive. Activation proceeds in several steps. First p62 cleavage activates the potential for low pH inducible fusion. Next the low pH which surrounds incoming virus in endosomes induces dissociation of the heterodimeric structure. This is followed by a rearrangement of E1 subunits into homotrimers which are fusion active.

A total of 61 eligible patients with metastatic cancer have been treated in a series of Phase II trials of the novel pentacyclic pyrroloquinone, fosquidone. Tumour types were colorectal (23), renal (21), and non small cell lung (17). No patient had received prior chemotherapy. The drug was given intravenously as a 20 min infusion at the dose of 120 mg-2 on days 1 to 5 every 3 weeks. Treatment was well tolerated; the only significant side effects being mild nausea and generalised musculo-skeletal pains. Response was assessed after two cycles of therapy. No patient achieved an objective partial response. A total of nine patients demonstrated stable disease for a median duration of 11 weeks. Using this schedule of administration, fosquidone has no significant antitumour activity in this group of tumours.