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Aim: There are few age‐ and fitness‐specific, evidence‐based guidelines for colorectal cancer surgery. The uptake of different assessment and optimization strategies is variable. The aim of this study was to explore healthcare professional opinion about these issues using a mixed methods design. Methods: Semi‐structured qualitative interviews were undertaken with healthcare professionals from a single UK region involved in the treatment, assessment and optimization of colorectal surgery patients. Interviews were analysed using the framework approach. An online questionnaire survey was subsequently designed and disseminated to UK surgeons to quantitatively assess the importance of interview themes. Descriptive statistics were used to analyse questionnaire data. Results: Thirty‐seven healthcare professionals out of 42 approached (response rate 88%) were interviewed across five hospitals in the south Yorkshire region. Three broad themes were developed: attitudes towards treatment of the older patient, methods of assessment of suitability and optimization strategies. The questionnaire was completed by 103 out of an estimated 256 surgeons (estimated response rate 40.2%). There was a difference in opinion regarding the role of major surgery in older patients, particularly when there is coexisting dementia. Assessment was not standardized. Access to optimization strategies was limited, particularly in the emergency setting. Conclusion: There is wide variation in the process of assessment and provision of optimization strategies in UK practice. Lack of evidence‐based guidelines, cost and time constraints restrict the development of services and pathways. Differences in opinion between surgeons towards patients with frailty or dementia may account for some of the variation in colorectal cancer outcomes.

Long noncoding RNAs (lncRNAs) are frequently associated with broad modulation of gene expression and thus provide the cell with the ability to synchronize entire metabolic processes. We used transcriptomic approaches to investigate whether the most abundant human cytomegalovirus-encoded lncRNA, RNA2.7, has this characteristic. By comparing cells infected with wild-type virus (WT) to cells infected with RNA2.7 deletion mutants, RNA2.7 was implicated in regulating a large number of cellular genes late in lytic infection. Pathway analysis indicated that >100 of these genes are associated with promoting cell movement, and the 10 most highly regulated of these were validated in further experiments. Morphological analysis and live cell tracking of WT- and RNA2.7 mutant-infected cells indicated that RNA2.7 is involved in promoting the movement and detachment of infected cells late in infection, and plaque assays using sparse cell monolayers indicated that RNA2.7 is also involved in promoting cell-to-cell spread of virus. Consistent with the observation that upregulated mRNAs are relatively A+U-rich, which is a trait associated with transcript instability, and that they are also enriched in motifs associated with mRNA instability, transcriptional inhibition experiments on WT- and RNA2.7 mutant-infected cells showed that four upregulated transcripts lived longer in the presence of RNA2.7. These findings demonstrate that RNA2.7 is required for promoting cell movement and viral spread late in infection and suggest that this may be due to general stabilization of A+U-rich transcripts. IMPORTANCE In addition to messenger RNAs (mRNAs), the human genome encodes a large number of long noncoding RNAs (lncRNAs). Many lncRNAs that have been studied in detail are associated with broad modulation of gene expression and have important biological roles. Human cytomegalovirus, which is a large, clinically important DNA virus, specifies four lncRNAs, one of which (RNA2.7) is expressed at remarkably high levels during lytic infection. Our studies show that RNA2.7 is required for upregulating a large number of human genes, about 100 of which are associated with cell movement, and for promoting the movement of infected cells and the spread of virus from one cell to another. Further bioinformatic and experimental analyses indicated that RNA2.7 may exert these effects by stabilizing mRNAs that are relatively rich in A and U nucleotides. These findings increase our knowledge of how human cytomegalovirus regulates the infected cell to promote its own success.

The endovascular aneurysm repair-2 (EVAR-2) trial suggested that EVAR in patients unfit for open surgical repair (OSR) failed to provide a significant overall survival advantage compared with conservative management. The aim is to compare survival and cost-effectiveness in patients with poor cardiopulmonary exercise test (CPET) metrics who underwent EVAR or were managed conservatively.A prospective database of all CPETs (1435 patients) performed to assess preoperative fitness for abdominal aortic aneurysm repair was maintained. A total of 350 patients deemed unfit for OSR underwent EVAR or were managed conservatively. A 1:1 propensity-matched analysis incorporating age, gender, anaerobic threshold, and aneurysm size was used to compare survival. Cost-effectiveness analysis was based on the economic model for the National Institute for Health and Care Excellence clinical guideline on abdominal aortic aneurysm treatment.Propensity matching produced 122 pairs of patients in the EVAR and conservative management groups. The median overall survival for the EVAR group was significantly longer than that for the conservative management group (84 vs 30 months, P .001). One-, three-, and five-year mortality in the EVAR group was 7%, 40%, and 68%, respectively, compared with 25%, 68%, and 82% in the conservative management group, all P .001. The increment cost-effectiveness ratio for EVAR was £8023 (US$11,644) per quality-adjusted life year gained compared with £430,602 (US$624,967) in the National Institute for Health and Care Excellence guideline, which is based on EVAR-2 results.EVAR offers a survival advantage and is cost-effective in selected patients deemed unfit for OSR based on CPET compared with conservative management.

The recent emergence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the underlying cause of Coronavirus Disease 2019 (COVID-19), has led to a worldwide pandemic causing substantial morbidity, mortality, and economic devastation. In response, many laboratories have redirected attention to SARS-CoV-2, meaning there is an urgent need for tools that can be used in laboratories unaccustomed to working with coronaviruses. Here we report a range of tools for SARS-CoV-2 research. First, we describe a facile single plasmid SARS-CoV-2 reverse genetics system that is simple to genetically manipulate and can be used to rescue infectious virus through transient transfection (without in vitro transcription or additional expression plasmids). The rescue system is accompanied by our panel of SARS-CoV-2 antibodies (against nearly every viral protein), SARS-CoV-2 clinical isolates, and SARS-CoV-2 permissive cell lines, which are all openly available to the scientific community. Using these tools, we demonstrate here that the controversial ORF10 protein is expressed in infected cells. Furthermore, we show that the promising repurposed antiviral activity of apilimod is dependent on TMPRSS2 expression. Altogether, our SARS-CoV-2 toolkit, which can be directly accessed via our website at https://mrcppu-covid.bio/, constitutes a resource with considerable potential to advance COVID-19 vaccine design, drug testing, and discovery science., To help meet the ensuing demand for COVID-19 reagents, this article presents an openly available ‘coronavirus toolkit’ (https://mrcppu-covid.bio) and describes the generation and validation of these tools, including a simple SARS-CoV-2 reverse genetics system and a near-comprehensive panel of SARS-CoV-2 antibodies.

Long non-coding RNAs (lncRNAs) are transcripts of >200 nucleotides that are not translated into functional proteins. Cellular lncRNAs have been shown to act as regulators by interacting with target nucleic acids or proteins and modulating their activities. We investigated the role of RNA1.2, which is one of four major lncRNAs expressed by human cytomegalovirus (HCMV), by comparing the properties of parental virus in vitro with those of deletion mutants lacking either most of the RNA1.2 gene or only the TATA element of the promoter. In comparison with parental virus, these mutants exhibited no growth defects and minimal differences in viral gene expression in human fibroblasts. In contrast, 76 cellular genes were consistently up- or down-regulated by the mutants at both the RNA and protein levels at 72 hours after infection. Differential expression of the gene most highly upregulated by the mutants (Tumor protein p63-regulated gene 1-like protein; TPRG1L) was confirmed at both levels by RT-PCR and immunoblotting. Consistent with the known ability of TPRG1L to upregulate IL-6 expression via NF-kappaB stimulation, RNA1.2 mutant-infected fibroblasts were observed to upregulate IL-6 in addition to TPRG1L. Comparable surface expression of TNF receptors and responsiveness to TNF-α in cells infected by the parental and mutant viruses indicated that activation of signalling by TNF-α is not involved in upregulation of IL-6 by the mutants. In contrast, inhibition of NF-kappaB activity and knockdown of TPRG1L expression reduced the extracellular release of IL-6 by RNA1.2 mutant-infected cells, thus demonstrating that upregulation of TPRG1L activates NF-kappaB. The levels of MCP-1 and CXCL1 transcripts were also increased in RNA1.2 mutant-infected cells, further demonstrating the presence of active NF-kappaB signalling. These results suggest that RNA1.2 plays a role in manipulating intrinsic NF-kappaB-dependent cytokine and chemokine release during HCMV infection, thereby impacting downstream immune responses.

peer-reviewed Equid herpesvirus 8 (EHV-8), formerly known as asinine herpesvirus 3, is an alpha herpesvirus that is closely related to equid herpesviruses 1 and 9 (EHV-1 and EHV-9). The pathogenesis of EHV-8 is relatively little studied and to date has only been associated with respiratory disease in donkeys in Australia and horses in China. A single EHV-8 genome sequence has been generated for strain Wh in China, but is apparently incomplete and contains frame shifts in two genes. In this study, the complete genome sequences of four EHV-8 strains isolated in Ireland between 2003 and 2015 were determined by Illumina sequencing. Two of these strains were isolated from cases of abortion in horses, and were misdiagnosed initially as EHV-1, and two were isolated from donkeys, one with neurological disease. The four genome sequences are very similar to each other, exhibiting greater than 98.4% nucleotide identity, and their phylogenetic clustering together demonstrated that genomic diversity is not dependent on the host. Comparative genomic analysis revealed 24 of the 76 predicted protein sequences are completely conserved among the Irish EHV-8 strains. Evolutionary comparisons indicate that EHV-8 is phylogenetically closer to EHV-9 than it is to EHV-1. In summary, the first complete genome sequences of EHV-8 isolates from two host species over a twelve year period are reported. The current study suggests that EHV-8 can cause abortion in horses. The potential threat of EHV-8 to the horse industry and the possibility that donkeys may act as reservoirs of infection warrant further investigation.

Background This study assessed the feasibility of a preoperative high-intensity interval training (HIT) programme in patients awaiting elective abdominal aortic aneurysm repair. Methods In this feasibility trial, participants were allocated by minimization to preoperative HIT or usual care. Patients in the HIT group were offered three exercise sessions per week for 4 weeks, and weekly maintenance sessions if surgery was delayed. Feasibility and acceptability outcomes were: rates of screening, eligibility, recruitment, retention, outcome completion, adverse events and adherence to exercise. Data on exercise enjoyment (Physical Activity Enjoyment Scale, PACES), cardiorespiratory fitness (anaerobic threshold and peak oxygen uptake), quality of life, postoperative morbidity and mortality, duration of hospital stay and healthcare utilization were also collected. Results Twenty-seven patients were allocated to HIT and 26 to usual care (controls). Screening, eligibility, recruitment, retention and outcome completion rates were 100 per cent (556 of 556), 43·2 per cent (240 of 556), 22·1 per cent (53 of 240), 91 per cent (48 of 53) and 79–92 per cent respectively. The overall exercise session attendance rate was 75·8 per cent (276 of 364), and the mean(s.d.) PACES score after the programme was 98(19) (‘enjoyable’); however, the intensity of exercise was generally lower than intended. The mean anaerobic threshold after exercise training (adjusted for baseline score and minimization variables) was 11·7 ml per kg per min in the exercise group and 11·4 ml per kg per min in controls (difference 0·3 (95 per cent c.i. –0·4 to 1·1) ml per kg per min). There were trivial-to-small differences in postoperative clinical and patient-reported outcomes between the exercise and control groups. Conclusion Despite the intensity of exercise being generally lower than intended, the findings support the feasibility and acceptability of both preoperative HIT and the trial procedures. A definitive trial is warranted. Registration number: ISRCTN09433624 (https://www.isrctn.com/).

A randomized controlled trial was used to evaluate the effects of a pro-social behavior after-school program called Mate-Tricks for nine and ten year old children and their parents living in an area of significant socioeconomic disadvantage. The children were randomly assigned to an intervention (n=220) or a control group (n=198). Children were compared on measures of pro-social behavior, anti-social behavior and related outcome measures. The trial found adverse effects on four outcomes among the intervention group compared to the control group: anti-social behavior increased on two different measures (d=+0.20) and (d=+0.18); child reported liberal parenting increased (d=+0.16); and child reported authoritarian parenting also increased (d=+0.20). In addition, parental participation was significantly associated with several program outcomes. It was concluded, that group based after-school behavior programs may have the potential to cause iatrogenic effects and must be designed, piloted, evaluated and implemented with a high degree of care.

A herpesvirus genome was sequenced directly from a biopsy specimen of a rectal lesion from a female common bottlenose dolphin. This genome sequence comprises a unique region (161,235 bp) flanked by multiple copies of a terminal repeat (4,431 bp) and contains 72 putative genes. The virus was named common bottlenose dolphin gammaherpesvirus 1.

Purpose: Intervention fidelity refers to the extent an experimental manipulation has been implemented as intended. Our aim was to evaluate the fidelity of high-intensity interval training (HIT) in patients awaiting repair of large abdominal aortic aneurysms.\ud \ud Methods: Following a baseline cardiopulmonary exercise test, 27 participants performed a hospital-based, supervised HIT intervention in the 4 weeks preceding surgery. The intervention was performed thrice weekly on a cycle ergometer and involved either 8 × 2-min intervals, each interspersed by 2-min recovery periods, or 4 × 4-min intervals interspersed with 4-min recovery periods. When surgery was delayed, participants undertook one maintenance HIT session per week until surgery. Session one power output was set to baseline anaerobic threshold power output and then increased on subsequent sessions until ratings of perceived exertion (RPE; Borg CR-10) for the legs (RPE-L) and sense of breathlessness/ chest (RPE-C) were hard (5) to very hard (7) at the end of each interval. For safety, power output was maintained or reduced if systolic blood pressure exceeded 180 mm Hg or heart rate exceeded 95% of maximum.\ud \ud Results: Overall session attendance across the 4-week HIT intervention was 74%. Seventeen participants met our compliance criteria of ≥75% of intervention sessions and all maintenance sessions. When compared to non-compliance, compliant participants had higher fitness, performed more HIT sessions and were able to exercise at higher exercise intensities with a lower proportion of exercise safety breaches. In the 17 compliant participants, the proportion of repetitions meeting the HIT criterion was 30% (RPE-L) and 16% (RPE-C). Mean repetition intensity was 4.1 ± 2.0 Arbitrary Units [AU] (RPE-L) and 3.5 ± 1.9 AU (RPE-C) with a within-subject variability of ±1.4 AU and ±1.6 AU, respectively. We observed higher RPE scores (~0.5 AU) following 2-min intervals when compared to 4-min intervals and exercise power output increased 23% across the 4-week HIT intervention. One participant experienced an adverse event but were still able to complete their remaining exercise sessions.\ud \ud Conclusions: Despite an inconsistent and lower than prescribed intensity, it is possible to exercise this high-risk patient population at moderate to hard intensities with a low risk of adverse events.\ud \ud Clinical Trial Registration: http://www.isrctn.com/, registration number ISRCTN09433624.

The World Health Organization recommends that all countries develop a cancer control program. Qatar is the first country in the Gulf Cooperation Council to develop such a plan, with its National Cancer Strategy 2011-2016. Three years into implementation, meaningful progress has been made, particularly in reducing patient waiting times, creating a multidisciplinary approach to cancer treatment, and fostering international research collaboration. Challenges include attracting sufficient numbers of trained health care workers, reaching a diverse population with messages tailored to their needs, and emphasizing cancer prevention and early detection in addition to research and treatment. Qatar's example shows that best practices developed in North America, Western Europe, and Australasia can be assimilated in a very different demographic and cultural context when such approaches are tailored to local characteristics and circumstances.

This paper builds on and contributes to work on learning and teaching in science, specifically in the area of thinking skills in primary (elementary) and early post-primary science education. It is based on the development and implementation of policy on thinking skills and personal capabilities in Northern Ireland (NI), where they form part of the statutory curriculum. The paper traces the development of a framework for thinking skills and personal capabilities, the adoption of the framework and its translation into policy, and through research on implementing the policy in school science. This critical exploration of theory-into policy-into practice demonstrates ways in which gaps in the process can be addressed, such as the higher-level involvement of teachers as researchers into policy development and implementation, as opposed to being merely ‘trained’ to implement new science learning and teaching policy. The contribution of pre-service teachers in the process provided an important element of the implementation process, particularly in relation to primary science. The article provides insight into issues such as how might we ‘teach’ thinking skills in conceptually rich science content, the relationship between thinking skills in science and other subjects, and the links between research and practice in children's science learning.

Johne's disease (JD), or paratuberculosis is a fatal enteritis of animals caused by infection with Mycobacterium avium subspecies paratuberculosis (Map). There may be a long subclinical phase with no signs of clinical disease. Diagnosis of JD is problematic and no test can reliably detect sub-clinical disease. Th1 responses to Map are believed to be activated first with a later switch to Th2 responses and progression to clinical disease. Detection of a cell-mediated response, indicated by interferon gamma (IFN-γ) produced in response to mycobacterial antigens, may give an early indication of infection. Crude extracts of Map (PPDj) have been used to detect the cell-mediated response, but more specific, quantifiable antigens would improve the test. Thirty Map-specific proteins were screened for their ability to raise a cell-mediated response in subclinically infected sheep. Four proteins were selected and tested using blood from subclinical animals and controls from a JD-free flock. Three proteins elicited IFN-γ levels which were higher in the subclinical group than in the control group, two were statistically significant. Thus these proteins have the ability to discriminate groups of infected and uninfected animals and may have use in diagnosis of JD.

Objectives To determine the feasibility of evidence-based design and use of low-cost virtual world environments for preparation and training in multi-agency, multi-site, major incident response. Methods A prospective cohort feasibility study was carried out. One pre-hospital, and two in-hospital major incident scenarios, were created in an accessible virtual world environment. 23 pre-hospital and hospital-based clinicians each took part in one of three linked major incident scenarios: a pre-hospital bomb blast site, focusing on the roles of the team leader and triage person; a blast casualty in a resuscitation room, focusing on the role of the trauma team leader; a hospital command and control scenario focusing on the role of the clinical major incident co-ordinator/silver commander. Participants supplied both quantitative and qualitative feedback. Results Using a systematic, evidence-based approach, three scenarios were successfully developed and tested using low-cost virtual worlds (Second Life and OpenSimulator). All scenarios were run to completion. 95% of participants expressed a desire to use virtual environments for future training and preparation. Pre-hospital responders felt that the immersive virtual environment enabled training in surroundings that would be inaccessible in real-life. Conclusions The feasibility and face/content validity of using low-cost virtual worlds for multi-agency major incident simulation has been established. Major incident planners and trainers should explore utilising this technology as an adjunct to existing methodologies. Future work will involve development of robust assessment metrics.

Summary Cancer prevalence is increasing in the Middle East, partly because of increased life expectancy and adoption of western lifestyle habits. Suboptimum delivery of health care also contributes to late diagnosis and poor survival of people with cancer. Public awareness of cancer risk is frequently low and misconceptions high, thereby preventing patients from seeking treatment early and constituting a substantial barrier to improvement of cancer outcomes. Screening programmes might have low uptake in Arab populations because of social and health beliefs about cancer. This review outlines the opportunities available to Middle Eastern countries and their emerging economies to learn from global experiences in cancer care, service provision, and research partnerships. The Middle East has begun to develop several health-care transformation programmes. Qatar, in particular, has published a National Health Strategy, in which cancer is one of the main commitments; this Strategy provides the focus of this review. The development of effective health-care strategies and evidence-based medicine directly linked to innovative cancer research is needed to improve cancer care. Although the full extent of the proposed solutions are not necessarily implementable in all Middle Eastern countries, wealthy states can lead derivation of population-specific approaches that could have effects throughout the region. Key challenges are outlined—namely, human capacity and training, subspecialisation of services, building on international cancer research initiatives, and the need for earlier diagnosis and awareness in the population. Countries in the Gulf Region (ie, countries bordering the Persian Gulf, including Iran, Iraq, Kuwait, Saudi Arabia, Bahrain, Qatar, UAE, and Oman) need to address these challenges to be at the forefront of integrated cancer care and research and ensure that the latest innovations and best possible care are delivered to their populations.

The Hamlyn Symposium is an annual international forum for clinicians, engineers and researchers to exchange ideas and explore new challenges and opportunities in medical robotics and allied technologies. The 5th Symposium was another success, due to the range of papers presented from leading international teams, and the growing workshop series, which is organised by teams of senior academics and young research fellows to further stimulate academic networking and collaboration. For this special issue, we have selected five representative manuscripts from the 52 papers from 11 countries presented at the Symposium, based on the initial review scores and the quality of the presentation during the meeting. They represent the unique multidisciplinary blend of the Symposium and our increasing focus on imaging and navigation, and usability by the surgeon to improve patient outcomes through technological innovation. The selected papers focus on novel developments in visualisation and navigation, and explore usability and skills assessment of new techniques. Visualisation and imaging are both important factors to consider in robotic surgery. The development and use of video augmentation for intraoperative image guidance for transoral robotic surgery is described by Liu et al. Using preoperative planning data, the team have demonstrated that the data can be registered to the intraoperative endoscopic view to augment and define targets, which will improve the operation through improved navigation, orientation and ultimately tumour resection. This has been piloted in situ to show improvements over and above simulated standard practice. Lee et al. explore improvements in navigation in vascular surgery, proposing a novel motionadaptive catheter navigation scheme to compensate for physiological motion and tortuous vessels. A simulated aortic branch cannulation procedure was used to demonstrate improved visualisation through dynamic shape modelling and real-time instantiation in conjunction with a reconstructed view of the catheter tip to enhance the usability for the surgeon. Improvements in efficiency and usability of robotic systems are increasingly being explored. In the paper by Simaan et al., a robotic system for single port access undergoes preliminary evaluation, demonstrating its design and functionality for basic tasks in minimally invasive surgery, manipulation, knot tying and visualisation/tracking. Ruiter et al. describe a novel robotic system that can be appended to a traditional flexible endoscope for advanced procedures, in particular those that need a team for complex and enhanced manoeuvrability. Initial results indicate that the robotic system reduces the time required to complete the investigation and that usability is enhanced from the physician’s perspective. Given the increased use of robotic systems, it is important to monitor and assess the surgeon’s skills as well as the technical developments. This is highlighted in the paper by Jun et al., which explores the use of a quantitative computer-based surgical performance evaluation scheme for assessing surgeons of varying levels. The Symposium would not be possible without the commitment and hard work of the programme and organising committees. We are also very grateful to all our distinguished invited speakers, particularly Professor Shigeo Hirose from Tokyo Institute of Technology, who provided an overview of ‘‘Biologically Inspired Robots: Snake-like, Spider-like Robots and Others’’, and Professor Richard Satava, who gave the inaugural Karl Storz–Harold Hopkins lecture on ‘‘Developing Next Generation Robots’’ that stimulated the panel debate.

This study builds on and contributes to work on assessment of children in primary school, particularly in science. Previous research has examined primary science assessment from different standpoints, but no studies have specifically addressed children's perspectives. This article provides additional insight into issues surrounding children's assessment in primary school and how the assessment of science might develop in England after the science SATs (Standard Assessment Tests) were abolished in 2009. Some research suggests that primary science assessment via SATs is a major reason for the observed decline in children's engagement with science in upper primary and lower secondary school. The analytic focus on engaging children as coresearchers to assist in the process of gathering informed views and interpreting findings from a large sample of children's views enables another contribution. The study, based on a survey of 1000 children in primary and secondary schools in England and Wales, reveals that despite being assessed under two different regimes (high-stakes national tests in England and moderated teacher assessment in Wales), children's views of science assessment are remarkably consistent. Most appreciate the usefulness of science assessment and value frequent, non-SATs testing for monitoring/improving science progress. There was a largely negative impact, however, of science assessment on children's well-being, particularly due to stress. The paper demonstrates that children provide an important perspective on assessment and that including their views can improve policy-making in relation to primary science assessment.

We resequenced the genome of equid herpesvirus 2 (EHV2) strain 86/67 and sequenced the genomes of EHV2 strain G9/92 and equid herpesvirus 5 (EHV5) strain 2-141/67. The most prominent genetic differences are the dissimilar locations of the interleukin-10 (IL-10)-like genes and the presence of an OX-2-like gene in EHV5 only.

Children and teachers may not think in the same way about particular science concepts. Such parallel lines of thought can compound children's confusion and misunderstanding as they learn science at primary school. The situation could be more acute when student teachers are teaching science, because of their limited experience of considering children's ideas. This paper investigates children's and student teachers’ ideas about certain science concepts: ‘animal’, ‘flower’, ‘living’, ‘force’ and ‘energy’. The ideas and understandings of 96 children and 168 student teachers were explored. Results showed that the student teachers and children had similar ideas about ‘flower’ and ‘animal’, whereas they evidenced very different responses to ‘living’, ‘energy’ and ‘force’. Implications for classroom practice are considered.

This research uses a strategic analytical tool in order to determine the key strengths and opportunities of the school subject Home Economics. The main strengths lie in the potential of a set of living skills, which this subject offers to pupils. The fact that the benefits of these skills are not recognised or valued is a major threat to the subject.

A latex agglutination test (LAT) has been developed for the diagnosis of contagious bovine pleuropneumonia (CBPP). The latex microspheres were coated with MmmSC polyclonal immunoglobulin G antiserum and detected MmmSC antigen in the serum of cattle infected with CBPP and in growth medium containing MmmSC. The specific antigen recognizsed by this test appeared to be the capsular polysaccharide (CPS). The LAT recognized all 23 strains of MmmSC examined in this study, with a sensitivity level of 2 ng of CPS, or the equivalent of 5 × 10 3 CFU, in a reaction volume of 0.03 ml. Therefore, rapid identification of MmmSC cultures should be possible. Agglutination was also observed with the related goat pathogens and “ Mycoplasma mycoides ” cluster members Mycoplasma mycoides subsp. mycoides large colony biotype (four of six strains positive) and Mycoplasma mycoides subsp. capri (three of six strains positive), in agreement with the suggestion that these latter two mycoplasmas may in fact represent a single species (although collectively exhibiting two capsular serotypes). Comparisons in diagnosis with the complement fixation test (CFT) were made by using African field sera from CBPP-infected cattle. After 2 (or 3) min of incubation, the test detected 55% (or 61%) of CFT-positive sera and 29% (or 40%) of CFT-negative sera, with an overall correlation in diagnosis of 62% (or 61%). The rates for false-positive diagnoses made by using “known” CBPP-negative sera from the United Kingdom were 3 or 13% after 2 or 3 min of incubation, respectively. The data agree with previous findings that some CBPP CFT-negative misdiagnoses may occur due to “antibody eclipsing” by excess circulating antigen. The LAT combines low cost and high specificity with ease of application in the field, without the need for any specialist training or equipment.

Infections of Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus (EEHV) can cause a rapid, highly lethal, hemorrhagic disease, which primarily affects juvenile animals up to the age of four years. So far, the majority of deaths have been attributed to infections with genotype EEHV1 or, more rarely, EEHV3 and EEHV4. Here, we report the pathological characteristics of the first fatality linked to EEHV5 infection, and describe the complete viral DNA sequence. Gross post-mortem and histological findings were indistinguishable from lethal cases previously attributed to other EEHV genotypes, and the presence of characteristic herpesviral inclusions in capillary endothelial cells at several sites was consistent with the diagnosis of acute EEHV infection. Molecular analysis confirmed the presence of EEHV5 DNA and was followed by sequencing of the viral genome directly from post-mortem material. The genome is 180,800 bp in size and contains 120 predicted protein-coding genes, five of which are fragmented and presumably nonfunctional. The seven families of paralogous genes recognized in EEHV1 are also represented in EEHV5. The overall degree of divergence (37%) between the EEHV5 and EEHV1 genomes, and phylogenetic analysis of eight conserved genes, support the proposed classification of EEHV5 into a new species (Elephantid herpesvirus 5).

The global epidemic of obesity continues to escalate. Obesity accounts for an increasing proportion of the international socioeconomic burden of noncommunicable disease. Online social networking services provide an effective medium through which information may be exchanged between obese and overweight patients and their health care providers, potentially contributing to superior weight-loss outcomes. We performed a systematic review and meta-analysis to assess the role of these services in modifying body mass index (BMI). Our analysis of twelve studies found that interventions using social networking services produced a modest but significant 0.64 percent reduction in BMI from baseline for the 941 people who participated in the studies' interventions. We recommend that social networking services that target obesity should be the subject of further clinical trials. Additionally, we recommend that policy makers adopt reforms that promote the use of anti-obesity social networking services, facilitate multistakeholder partnerships in such services, and create a supportive environment to confront obesity and its associated noncommunicable diseases.

Introduction In patients with large abdominal aortic aneurysm (AAA), open surgical or endovascular aneurysm repair procedures are often used to minimise the risk of aneurysm-related rupture and death; however, aneurysm repair itself carries a high risk. Low cardiopulmonary fitness is associated with an increased risk of early post-operative complications and death following elective AAA repair. Therefore, fitness should be enhanced before aneurysm repair. High-intensity interval exercise training (HIT) is a potent, time-efficient strategy for enhancing cardiopulmonary fitness. Here, we describe a feasibility study for a definitive trial of a pre-operative HIT intervention to improve post-operative outcomes in patients undergoing elective AAA repair. Methods and analysis A minimum of 50 patients awaiting elective repair of a 5.5–7.0 cm infrarenal AAA will be allocated by minimisation to HIT or usual care control in a 1:1 ratio. The patients allocated to HIT will complete three hospital-based exercise sessions per week, for 4 weeks. Each session will include 2 or 4 min of high-intensity stationary cycling followed by the same duration of easy cycling or passive recovery, repeated until a total of 16 min of high-intensity exercise is accumulated. Outcomes to be assessed before randomisation and 24–48 h before aneurysm repair include cardiopulmonary fitness, maximum AAA diameter and health-related quality of life. In the post-operative period, we will record destination (ward or critical care unit), organ-specific morbidity, mortality and the durations of critical care and hospital stay. Twelve weeks after the discharge, participants will be interviewed to reassess quality of life and determine post-discharge healthcare utilisation. The costs associated with the exercise intervention and healthcare utilisation will be calculated. Ethics and dissemination Ethics approval was secured through Sunderland Research Ethics Committee. The findings of the trial will be disseminated through peer-reviewed journals, and national and international presentations. Trial registration Current Controlled Trials ISRCTN09433624.

Mice deficient for fibroblast growth factor (Fgf)R2-IIIb show a block in thymic growth after embryonic day 12.5, a stage that just precedes its detection in thymic epithelial cells. Fgf7 and Fgf10, the main ligands for FgfR2-IIIb, are expressed in the mesenchyme surrounding the thymic epithelial primordium, and Fgf10-deficient mice also exhibit impaired thymic growth. Hence, Fgf signaling is essential for thymic epithelial proliferation. In addition to the proliferative block, most thymic epithelial cells fail to progress from an immature cytokeratin 5-positive to a cytokeratin 5-negative phenotype. Nevertheless, sufficient epithelial cell differentiation occurs in the severely hypoplastic thymus to allow the development of CD4/CD8-double-positive thymocytes and a very small number of single-positive thymocytes expressing TCRs.

A highly lethal hemorrhagic disease associated with infection by elephant endotheliotropic herpesvirus (EEHV) poses a severe threat to Asian elephant husbandry. We have used high-throughput methods to sequence the genomes of the two genotypes that are involved in most fatalities, namely, EEHV1A and EEHV1B (species Elephantid herpesvirus 1 , genus Proboscivirus , subfamily Betaherpesvirinae , family Herpesviridae ). The sequences were determined from postmortem tissue samples, despite the data containing tiny proportions of viral reads among reads from a host for which the genome sequence was not available. The EEHV1A genome is 180,421 bp in size and consists of a unique sequence (174,601 bp) flanked by a terminal direct repeat (2,910 bp). The genome contains 116 predicted protein-coding genes, of which six are fragmented, and seven paralogous gene families are present. The EEHV1B genome is very similar to that of EEHV1A in structure, size, and gene layout. Half of the EEHV1A genes lack orthologs in other members of subfamily Betaherpesvirinae , such as human cytomegalovirus (genus Cytomegalovirus ) and human herpesvirus 6A (genus Roseolovirus ). Notable among these are 23 genes encoding type 3 membrane proteins containing seven transmembrane domains (the 7TM family) and seven genes encoding related type 2 membrane proteins (the EE50 family). The EE50 family appears to be under intense evolutionary selection, as it is highly diverged between the two genotypes, exhibits evidence of sequence duplications or deletions, and contains several fragmented genes. The availability of the genome sequences will facilitate future research on the epidemiology, pathogenesis, diagnosis, and treatment of EEHV-associated disease.

Localization of mRNAs, a crucial step in the early development of some animals, has been shown to be directed by cis-acting elements that presumably interact with localization factors. Here we identify a protein, exl, that binds to BLE1, an RNA localization element from the Drosophila bicoid mRNA. Using mutations in BLE1, we demonstrate a correlation between in vitro exl binding and one phase of in vivo localization directed by BLE1, implicating exl in that localization event. Furthermore, the same phase of localization is disrupted in exuperantia mutants, suggesting that exl and exuperantia proteins interact. Identification of a protein that binds specifically to an mRNA localization element and acts in mRNA localization opens the way for a biochemical analysis of this process.

Oskar (osk) protein directs the deployment of nanos (nos), the posterior body-patterning morphogen in Drosophila. To avoid inappropriate activation of nos, osk activity must appear only at the posterior pole of the oocyte, where the osk mRNA becomes localized during oogenesis. Here, we show that translation of osk mRNA is, and must be, repressed prior to its localization; absence of repression allows osk protein to accumulate throughout the oocyte, specifying posterior body patterning throughout the embryo. Translational repression is mediated by an ovarian protein, bruno, that binds specifically to bruno response elements (BREs), present in multiple copies in the osk mRNA 3′UTR. Addition of BREs to a heterologous mRNA renders it sensitive to translational repression in the ovary.

RÉSUMÉEn dépit de la reconnaissance du rôle d'information de la famille auprès des personnes âgées fragiles, il n'existe aucune entente sur la composition des familles assurant la prestation de soins. Les auteurs discutent de l'idéologie de l'aide aux aines par la famille et le degré de connaissance sur sa composition. Us proposent que ces familles présentent des caractéristiques actuelles et potentielles. En se fondant sur l'hypothèse que le concept de «la composition de la famille» est le résultat d'une construction sociale, les auteurs démontrent qu'il est essentiel de comprendre «la composition de la famille» selon l'optique des principaux prestateurs de soins afin d'évaluer la nature de l'appui familial. L'ouvrage remet en question la notion que la famille assurant la prestation de soins se compose des proches parents. Les auteurs soutiennent que le statu quo, où une perception simpliste de la famille offrant des soins est utilisée afin d'exercer des pressions sur les familles pour fournir plus de soins, n'a pas d'avenir.

This chapter reviews research into children’s attitudes toward primary science over the past 40 years. The authors discuss, synthesize, and critique methods and findings from studies to date. We look to the future and consider new directions in attitudinal research work with children including participatory approaches. Relevant literature in relation to primary children’s attitudes to science is also discussed. The literature considered reflects two major aspects of science: children’s attitudes to the science topics taught, and their interest in and enjoyment of science lessons.

This chapter examines a model of coteaching in which student teachers and classroom teachers learn together first, for example, on a continuing professional development (CPD) programme and then implement that learning together as coteachers in the classroom. Teachers from 25 primary schools (covering all areas of Northern Ireland) and the student teachers, with whom they would be placed, attended a CPD course aimed at enhancing creativity, thinking and enquiry in primary science learning and teaching. The focus was on expanding teacher and student teacher agency by empowering them to involve children more in their own learning. Research shows that primary teachers who are not qualified in science tend to keep control of the knowledge and to discourage children from asking questions because of a lack of confidence in their own subject knowledge. Many of the activities in the CPD workshops were of the ‘black box’ type with no ‘correct’ answers. Data collection incorporated focus groups, individual interviews and confidence/attitudinal audits with teachers, student teacher and children. A sample of coteaching lessons was video recorded and examined together with the reflection and presentation workshops. The findings showed that the combination of relevant and exciting workshop activities designed to empower teachers to enable children to ‘lead’ their science learning, and the coteaching of science in the classroom, changed the way these teachers approached their science teaching. The success of this work was a result of the solidarity built up by group members learning together, expansion of teacher and student teacher agency through coteaching, which helped them increase children’s interest and engagement with science. A specific strength of this approach lies in its sustainability. One of the main issues with CPD is sustainability. Very often teachers find it difficult to implement new ideas and approaches and highlight lack of time, existing curricular pressures and lack of support as problems. In the current programme, we address the issue of sustainability by incorporating science student teachers in the CPD. The student teachers provided specific support in terms of science expertise in coteaching, coplanning (which helped address issues around lack of time) and co-reflection. Both teachers and student teachers developed professionally as they made sustainable changes to their teaching approaches and how they think about teaching science.

Spermatogenesis is a complex process that cannot be modelledin vitro. The somatic Sertoli cells (SCs) within the seminiferous tubules perform a key role in supporting maturation of germ cells (GCs). Progress has been made in determining what aspects of SC function are critical to maintenance of fertility by developing rodent models based on the Cre/LoxP system; however, this is time-consuming and is only applicable to mice. The aim of the present study was to establish methods for direct injection of adenoviral vectors containing shRNA constructs into the testis as a way of inducing target-selective knock-downin vivo. We describe here a series of experiments using adenovirus expressing a green fluorescent protein (GFP) transgene. Injection via the efferent ductules resulted in SC-specific expression of GFP; expression levels paralleled the amount of infective viral particles injected. At the highest doses of virus seminiferous tubule architecture were grossly disturbed and immune cell invasion noted. At lower concentrations, the expression of GFP was variable/negligible, the seminiferous tubule lumen was maintained but stage-dependent GC loss and development of numerous basal vacuoles was observed. These resembled intercellular dilations of SC junctional complexes previously described in rats and may be a consequence of disturbances in SC function due to interaction of the viral particles with the coxsackie/adenovirus receptor that is a component of the junctional complexes within the blood testis barrier. In conclusion, intra-testicular injection of adenoviral vectors disturbs SC functionin vivoand future work will therefore focus on the use of lentiviral delivery systems.

Eosinophilia is a well documented feature of helminth infections but the precise nature of the interaction between parasite and eosinophil remains an enigma. This paper describes experiments demonstrating that ruminant gastrointestinal trichostrongyles produce potent chemoattractant activity for ovine bone marrow-derived eosinophils in vitro. This activity was initially identified as a constituent of whole worm extracts of third and fourth larval (L3, L4), and adult stages of Teladorsagia circumcincta, and adult Haemonchus contortus. Similar activity was detected in excretory/secretory (E/S) material derived from live T. circumcincta L3. Subsequently, by adapting the assay technique to incorporate live worms directly into the system, it was shown that L3 of both T. circumcincta and H. contortus produced eosinophil chemoattractant activity. In contrast, neither whole worm extracts, or E/S preparations from mixed stages of the free-living nematode Caenorhabditis elegans contained eosinophil chemoattractant activity, and there was no evidence of chemoattractant production by live C. elegans. The results described are challenging to the traditional dogma that eosinophils are host-protective effector cells, and raise the intriguing possibility that ovine nematodes actively encourage recruitment of eosinophils. Local eosinophil-mediated mucosal damage, comparable to that seen in the asthmatic lung, may then provide a permissive local microenvironment for the parasite. Moreover, if they prove important for pathogenicity, nematode chemoattractants could offer future potential as novel therapeutic targets.

ERBB2 is a receptor tyrosine kinase present on the basolateral membrane of polarized epithelia and has important functions in organ development and tumorigenesis. Using mutagenic analyses and Madin-Darby canine kidney (MDCK) cells, we have investigated the signals that regulate basolateral targeting of ERBB2. We show that basolateral delivery of ERBB2 is dependent on a novel bipartite juxtamembrane sorting signal residing between Gln-692 and Thr-701. The signal shows only limited sequence homology to known basolateral targeting signals and is both necessary and sufficient for correct sorting of ERBB2. In addition we demonstrate that this motif can function as a dominant basolateral targeting signal by its ability to redirect the apically localized P75 neurotrophin receptor to the basolateral membrane domain of polarized epithelial cells. Interestingly, LLC-PK1 cells, which are deficient for the micro 1B subunit of the AP1B adaptor complex, missort a large proportion of ERBB2 to the apical membrane domain. This missorting can be partially corrected by the introduction of micro 1B, suggesting a possible role for AP1B in ERBB2 endosomal trafficking. Furthermore, we find that the C-terminal ERBIN binding domain of ERBB2 is not necessary for its basolateral targeting in MDCK cells.

Health status is acknowledged by nursing theory as a factor in the probability of health behavior changes. Yet few studies have addressed the health-related barriers encountered by chronically ill elderly patients in primary care clinics who are trying to increase their physical activity. This study used self- and interviewer-administered instruments to assess potential barriers to physical activity in a sample of 60- to 80-year-old patients entering a walking program. Pain, fatigue, and mobility and sensory impairments were prevalent and could be significant barriers to participation. The authors present specific suggestions for helping patients overcome these barriers.