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Objective: To explore the experiences of women in Scotland who return home to complete medical termination of pregnancy (TOP) ≤63 days of gestation, after being administered with mifepristone and misoprostol at an NHS TOP clinic., Design: Qualitative interview study., Setting: One National Health Service health board (administrative) area in Scotland., Population or Sample: Women in Scotland who had undergone medical TOP ≤63 days, and self-managed passing the pregnancy at home; recruited from three clinics in one NHS health board area between January and July 2014., Methods: In-depth, semi-structured interviews with 44 women in Scotland who had recently undergone TOP ≤63 days of gestation, and who returned home to pass the pregnancy. Data were analysed thematically using an approach informed by the Framework method., Main Outcome Measures: Women's experiences of self-management of TOP ≤63 days of gestation., Results: Key themes emerging from the analysis related to self-administration of misoprostol in clinic; reasons for choosing home self-management; facilitation of self-management and expectation-setting; experiences of getting home; self-managing and monitoring treatment progress; support for self-management (in person and remotely); and pregnancy self-testing to confirm completion., Conclusions: Participants primarily found self-administration of misoprostol and home self-management to be acceptable and/or preferable, particularly where this was experienced as a decision made jointly with health professionals. The way in which home self-management is presented to women at clinic requires ongoing attention. Women could benefit from the option of home administration of misoprostol., Tweetable Abstract: Women undergoing medical TOP 63 days found home self-management to be acceptable and/or preferable., (© 2017 The Authors. BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley& Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Objective: To examine the experiences of women seeking more than one termination of pregnancy (TOP) within 2 years., Design: Mixed methods study., Setting: Six TOP services across Scotland., Sample: Women presenting for TOP between July and December 2015., Methods: Descriptive and inferential analysis of quantitative survey data, thematic analysis of qualitative interview data and integrative analysis. In quantitative analysis, multinomial logistic regression was used to compare three groups: previous TOP within 2 years, previous TOP beyond 2 years and no previous TOP., Main Outcome Measures: Characteristics and experiences of women seeking TOP., Results: Of 1662 questionnaire respondents, 14.6% (n = 242) and 19.8% (n = 329) reported previous TOP within and beyond 2 years, respectively. The previous TOP within 2 years group was significantly less likely to own their accommodation than the no previous TOP group (adjusted odds ratio [aOR] 0.34, 95% CI: 0.18-0.62) and previous TOP beyond 2 years group (aOR: 0.44, 95% CI: 0.23-0.85); and more likely to report inconsistent (aOR: 1.63, 95% CI: 1.04-2.57; aOR: 1.95, 95% CI: 1.16-3.28) and consistent (aOR: 2.13, 95% CI: 1.39-3.26; aOR: 1.71, 95% CI: 1.07-2.76) contraceptive use than the no previous TOP and previous TOP within 2 years groups, respectively. Twenty-three women from the previous TOP within 2 years group were interviewed. Qualitative and integrative analyses highlight issues relating to contraceptive challenges, intimate partner violence, life aspirations and socio-economic disadvantage., Conclusions: Women undergoing more than one TOP within 2 years may experience particular challenges and vulnerabilities. Service provision should recognise this and move away from stigmatising discourses of 'repeat abortion'., Funding: Scottish Government., Tweetable Abstract: Women having two or more terminations of pregnancy in 2 years may face key challenges/vulnerabilities including intimate partner violence and socio-economic disadvantage., (© 2017 The Authors BJOG: An International Journal of Obstetrics and Gynaecology published by John Wiley & Sons Ltd on behalf of Royal College of Obstetricians and Gynaecologists.)

Background: In 2016, 29% of pedestrians killed or seriously injured on the roads in Great Britain were under 15 years of age. Children with Developmental Coordination Disorder (DCD), a chronic disorder affecting the acquisition and execution of motor skills, may be more vulnerable at the roadside than typically developing (TD) children. Current methods used to teach road safety are typically knowledge-based and do not necessarily improve behaviour in real traffic situations. Virtual reality road crossing tasks may be a viable alternative., Aims/methods: The present study aimed to test the road crossing accuracy of children with and without DCD in virtual reality tasks that varied the viewpoint to simulate the teaching methods currently used in road safety educational programmes. Twenty-one children with DCD and twenty-one age and gender matched TD peers were required to locate the safest road crossing sites in two conditions: allocentric (aerial viewpoint) and egocentric (first-person viewpoint)., Procedures/outcomes: All children completed both conditions and were required to navigate either themselves or an avatar across the road using the safest crossing route. The primary outcome was accuracy defined as the number of trials, out of 10, on which the child successfully identified and used the safest crossing route., Results/conclusions: Children with DCD performed equally poorly in both conditions, while TD children were significantly more accurate in the egocentric condition. This difference cannot be explained by self-reported prior road crossing education, practice or confidence., Implications: While TD children may benefit from the development of an egocentric virtual reality road crossing task, multimodal methods may be needed to effectively teach road safety to children with DCD., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The ability to safely cross a road is a perceptual-motor skill that involves coordination between a pedestrian's perception of the approaching vehicles and their locomotive capability to execute the road crossing action. Developmental Coordination Disorder (DCD) is a chronic disorder that is characterised by significant motor difficulties that impact on daily living, including a reduced ability to perform visually guided actions. A total of 25 typically developing primary school aged children and 25 age- and gender-matched children with DCD were presented with a virtual desktop task that required them to select suitable temporal crossing gaps between vehicles a stream of traffic approaching at either 20mph, 30mph or 40mph from the near-side (one-lane) or both near+far-sides (two-lane). A best-PEST staircase procedure was used to measure the temporal gaps that children accepted and the maximum likelihood value was taken after nine reversals as each participant's threshold. Typically developing children accepted temporal gaps that were sufficient to execute a safe crossing for vehicles approaching at 20mph and 30mph, but insufficient for vehicles approaching at 40mph. In contrast, children with DCD selected insufficient temporal crossing gaps across all approach speeds, which if translated to the roadside would have resulted in collision. These findings add to our understanding of the difficulties that children with DCD appear to have with visually guided behaviour and suggest the potential impact on one aspect of daily functioning that could have significant consequences., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Abortions in general, and second trimester abortions in particular, are experiences which in many contexts have limited sociocultural visibility. Research on second trimester abortion worldwide has focused on a range of associated factors including risks and acceptability of abortion methods, and characteristics and decision-making of women seeking the procedure. Scholarship to date has not adequately addressed the embodied physicality of second trimester abortion, from the perspective of women's lived experiences, nor how these experiences might inform future framings of abortion. To progress understandings of women's embodied experiences of second trimester abortion, we draw on the accounts of 18 women who had recently sought second trimester abortion in Scotland. We address four aspects of their experiences: later recognition of pregnancy; experiences of a second trimester pregnancy which ended in abortion; the "labour" of second trimester abortion; and the subsequent bodily transition. The paper has two key aims: Firstly, to make visible these experiences, and to consider how they relate to dominant sociocultural narratives of pregnancy; and secondly, to explore the concept of "liminality" as one means for interpreting them. Our findings contribute to informing future research, policy and practice around second trimester abortion. They highlight the need to maintain efforts to reduce silences around abortion and improve equity of access.

'Body work' has emerged at the nexus of sociologies of work and bodies as a means of conceptualising work focusing on the bodies of others. This article utilises this analytical tool in the context of contemporary abortion work. Abortion provision in Britain has seen significant change in the last 25 years, paralleling developments in medical methods, and the option for women under nine weeks' gestation to complete the abortion at home. These shifts raise questions around how abortion work is experienced by those who do it. We apply the conceptual lens of body work to data drawn from in-depth interviews with 37 health professionals involved in abortion provision, to draw out the character, constraints and challenges of contemporary abortion work. We explore three key themes: the instrumental role of emotional labour in facilitating body work; the temporality of abortion work; and bodily proximity, co-presence and changes in provision. By drawing on the conceptual frame of body work, we illuminate the dynamics of contemporary abortion work in Britain and, by introducing the idea of 'body work-by-proxy', highlight ways in which this context can be used to expand the conceptual boundaries of body work., (© 2016 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL.)

Objective: To explore the experiences of women from a remote and rural setting who had a termination of pregnancy (TOP), in relation to any barriers they may have experienced trying to access TOP., Design: Qualitative interview study., Setting: Scottish Highlands and Western Isles., Population: Women who had undergone TOP in the Scottish Highlands National Health Service between October 2014 and May 2015., Methods: Sixteen semi-structured, audio-recorded telephone interviews were conducted by a researcher with women who had consented to be interviewed at their initial assessment. Six stages of thematic analysis were followed to explore themes in and across participant accounts., Main Outcome Measures: Themes derived from interview transcripts., Results: Four themes emerged relating to barriers to access and experience: (1) the impact of travel for TOP, (2) temporal factors unique to this population and how they affected women, (3) the attitude of health professionals, notably general practitioners, as a result of local culture, and (4) stigma surrounding TOP and the expectation that abortion will be traumatising., Conclusion: Women in remote and rural areas experience barriers to accessing TOP. Prompt referrals, more providers of TOP and tackling stigma associated with TOP could make delivery of this service more equitable and improve women's journey through TOP., Tweetable Abstract: Women in remote and rural areas of Scotland face multiple barriers to accessing termination of pregnancy., (© 2016 Royal College of Obstetricians and Gynaecologists.)

Objective: To examine experiences of contraceptive care from the perspective of health professionals and women seeking abortion, in the contexts of hospital gynaecology departments and a specialist sexual and reproductive health centre (SRHC)., Materials and Methods: We conducted in-depth semistructured interviews with 46 women who had received contraceptive care at the time of medical abortion (gestation ≤9weeks) from one SRHC and two hospital gynaecology-department-based abortion clinics in Scotland. We also interviewed 25 health professionals (nurses and doctors) involved in abortion and contraceptive care at the same research sites. We analysed interview data thematically using an approach informed by the Framework method, and comparison was made between the two clinical contexts., Results: Most women and health professionals felt that contraceptive counselling at abortion was acceptable and appropriate, if provided in a sensitive, nonjudgmental way. Participants framed contraceptive provision at abortion as significant primarily as a means of preventing subsequent unintended conceptions. Accounts of contraceptive decision making also presented tensions between the priorities of women and health professionals, around 'manoeuvring' women towards contraceptive uptake. Comparison between clinical contexts suggests that women's experiences may have been more positive in the SRHC setting., Conclusions: Whilst abortion may be a theoretically and practically convenient time to address contraception, it is by no means an easy time to do so and requires considerable effort and expertise to be managed effectively. Training for those providing contraceptive care at abortion should explicitly address potential conflicts between the priorities of health professionals and women seeking abortion., Implications: This paper offers unique insight into the detail of women and health professionals' experiences of addressing contraception at the time of medical abortion. The comparison between hospital and community SRHC contexts highlights best practise and areas for improvement relevant to a range of settings., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Because of deteriorating exocrine function, malabsorption renders chronic pancreatitis (CP) patients at risk of osteoporosis and fracture. However, the pathogenesis of low bone mineral density (BMD) has not been characterized. We hypothesized that bone turnover is elevated in CP, and we sought to investigate an association between bone metabolism and systemic inflammation., Methods: Twenty-nine CP patients and twenty-nine matched controls were recruited. Bone-turnover markers procollagen 1 amino-terminal propeptide (P1NP), OC (osteocalcin; bone formation markers), and carboxy-terminal telopeptide of type I collagen (CTX-I; bone resorption marker) were measured along with vitamin D (25-hydroxyvitamin D, 25OHD), parathyroid hormone (PTH), interleukin 6 (IL-6), high-sensitivity (hs) C-reactive protein (CRP), and sex/thyroid hormones. BMD was measured by dual-energy X-ray absorptiometry. Smoking status was noted., Results: Of the CP patients, 31% had osteoporosis and 44.8% osteopenia (controls: 6.9 and 51.7%, respectively; P=0.019). BMD was lower for patients at the lumbar spine (P=0.014) and femoral neck (P=0.029). Patients had elevated bone formation (P1NP (P=0.0068), OC (P=0.033)) and bone resportion (CTX-I (P=0.016)) compared with controls. Patients had lower 25OHD compared with controls (P=0.0126) and higher inflammatory markers (hsCRP, P=0.0013). Sex and thyroid hormone levels were similar. Patients with lowest 25OHD levels had highest P1NP. In a multivariable model, age, PTH, and smoking were predictive of 25OHD. Patients with osteoporosis had higher P1NP, PTH, and IL-6 and lower 25OHD. Using analysis of variance, inflammation (hsCRP) was highest in those with lowest 25OHD and lowest BMD., Conclusions: For the first time, bone turnover was shown to be abnormal in CP, and importantly, an association between low 25-OHD, smoking, and systematic inflammation was identified. Moreover, those with osteoporosis had the highest systemic inflammation. Together these factors provide an avenue for potential modification of risk factors, which may ultimately reduce bone loss and avert fractures in this group.

Background/aims: CXCL12, acting via one of its G protein-coupled receptors, CXCR4, is a chemoattractant for a broad range of cell types, including several types of cancer cells. Elevated expression of CXCR4, and its ligand CXCL12, play important roles in promoting cancer metastasis. Cancer cells have the potential for rapid and unlimited growth in an area that may have restricted blood supply, as oxidative stress is a common feature of solid tumors. Recent studies have reported that enhanced expression of cytosolic superoxide dismutase (SOD1), a critical enzyme responsible for regulation of superoxide radicals, may increase the aggressive and invasive potential of malignant cells in some cancers., Methods: We used a variety of biochemical approaches and a prostate cancer cell line to study the effects of SOD1 on CXCR4 signaling., Results: Here, we report a direct interaction between SOD1 and CXCR4. We showed that SOD1 interacts directly with the first intracellular loop (ICL1) of CXCR4 and that the CXCL12/CXCR4-mediated regulation of AKT activation, apoptosis and cell migration in prostate cancer (PCa) cells is differentially modulated under normal versus hypoxic conditions when SOD1 is present., Conclusions: This study highlights a potential new regulatory mechanism by which a sensor of the oxidative environment could directly regulate signal transduction of a receptor involved in cancer cell survival and migration., (© 2015 The Author(s) Published by S. Karger AG, Basel.)

During glacial periods of the Late Pleistocene, an abundance of proxy data demonstrates the existence of large and repeated millennial-scale warming episodes, known as Dansgaard-Oeschger (DO) events. This ubiquitous feature of rapid glacial climate change can be extended back as far as 800,000 years before present (BP) in the ice core record, and has drawn broad attention within the science and policy-making communities alike. Many studies have been dedicated to investigating the underlying causes of these changes, but no coherent mechanism has yet been identified. Here we show, by using a comprehensive fully coupled model, that gradual changes in the height of the Northern Hemisphere ice sheets (NHISs) can alter the coupled atmosphere-ocean system and cause rapid glacial climate shifts closely resembling DO events. The simulated global climate responses--including abrupt warming in the North Atlantic, a northward shift of the tropical rainbelts, and Southern Hemisphere cooling related to the bipolar seesaw--are generally consistent with empirical evidence. As a result of the coexistence of two glacial ocean circulation states at intermediate heights of the ice sheets, minor changes in the height of the NHISs and the amount of atmospheric CO2 can trigger the rapid climate transitions via a local positive atmosphere-ocean-sea-ice feedback in the North Atlantic. Our results, although based on a single model, thus provide a coherent concept for understanding the recorded millennial-scale variability and abrupt climate changes in the coupled atmosphere-ocean system, as well as their linkages to the volume of the intermediate ice sheets during glacials.

Context: Except in the presence of significant medical indications, the legal limit for abortion in Great Britain is 24 weeks' gestation. Nevertheless, abortion for nonmedical reasons is not usually provided in Scotland after 18-20 weeks, meaning women have to travel to England for the procedure., Methods: In-depth interviews were conducted with 23 women presenting for "later" abortions (i.e., at 16 or more weeks' gestation) in Scotland. Participants were women who sought an abortion at a participating National Health Service clinic between January and July 2013. Interviews addressed reasons for and consequences of later presentation, as well as women's experiences of abortion. Thematic analysis attended to emerging issues and employed the conceptual tool of candidacy., Results: Delayed recognition of pregnancy, changed life circumstances and conflicting candidacies for motherhood and having an abortion were common reasons for women's presentation for later abortion. Women perceived that the resources required to travel to England for a later abortion were potential barriers to access, and felt that such travel was distressing and stigmatizing. Participants who continued their pregnancy did so after learning they were at a later gestational age than expected or after receiving assurances of support from partners, friends or family., Conclusions: Reasons for seeking later abortion are complex and varied among women in Scotland, and suggest that reducing barriers to access and improving local provision of such abortions are a necessity. The candidacy framework allows for a fuller understanding of the difficulties involved in obtaining abortions., (© 2014 The Authors. Perspectives on Sexual and Reproductive Health published by Wiley Periodicals, Inc. on behalf of The Guttmacher Institute.)

Purpose: The protease inhibitor bortezomib attenuates the action of NF-κB and has shown preclinical activity alone and in combination with chemotherapy., Design: A Phase I dose-escalation study was performed administering bortezomib (0.7, 1.0, 1.3 and 1.6 mg m(-2) on days 1 and 8 from cycle 2 onwards) in combination with Epirubicin 50 mg m(-2) intravenously on day 1, Carboplatin AUC 5 day 1 and Capecitabine 625 mg m(-2) BD days 1-21 every 21 days (VECarboX regimen), in patients with advanced oesophagogastric adenocarcinoma. The primary objective was to define the maximum tolerated dose (MTD) of Bortezomib when combined with ECarboX., Results: 18 patients received bortezomib 0.7 (n = 6), 1.0 (n = 3), 1.3 (n = 6) and 1.6 mg m(-2) (n = 3) and a protocol amendment reducing the capecitabine dose to 500 mg m(-2) BD was enacted due to myelotoxicity. Common treatment-related non-haematological adverse events of any grade were fatigue (83.3 %), anorexia (55.6 %), constipation (55.6 %) and nausea (55.6 %). Common Grade 3/4 haematological toxicities were neutropenia (77.8 %) and thrombocytopenia (44.4 %). Objective responses were achieved in 6 patients (33.3 %) and a further 5 patients (27.8 %) had stable disease for >8 weeks., Conclusions: The addition of Bortezomib to ECarboX is well tolerated and response rates are comparable with standard chemotherapy.

Developmental coordination disorder (DCD) affects around 5% of children and commonly overlaps with other developmental disorders including: attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs) and specific language impairment (SLI). There is evidence to demonstrate the wide-ranging impact on all areas of functioning including psychiatric and learning domains. There is increasing evidence of the continuing impact into adulthood and the long-term negative effects on relationships and employment. There is a need for early identification and intervention to limit the likelihood of these secondary consequences from emerging. This paper addresses the diagnosis of DCD.

The media play a significant part in shaping public perceptions of health issues, and abortion attracts continued media interest. Detailed examination of media constructions of abortion may help to identify emerging public discourse. Qualitative content analysis was used to examine if and how the print media in contributes to the stigmatisation of abortion. Articles from seven British and five Scottish national newspapers from 2010 were analysed for overall framings of abortion and emergent themes, including potentially stigmatising discursive constructs and language. Abortion was found to be presented using predominantly negative language and discursive associations as 'risky', and in association with other 'discredited' social practices. Key perspectives were found to be absent or marginalised, including those of women who have sought abortion. Few articles framed abortion as a positive and legitimate choice. Negative media representations of abortion contribute to the stigmatisation of the procedure and of women who have it, and reflect a discrediting of women's reproductive decision-making. There is a need to challenge the notion that abortion stigma is inevitable, and to encourage positive framings of abortion in the media and other public discourse.

The nucleus of the Milky Way is known to harbour regions of intense star formation activity as well as a supermassive black hole. Recent observations have revealed regions of γ-ray emission reaching far above and below the Galactic Centre (relative to the Galactic plane), the so-called 'Fermi bubbles'. It is uncertain whether these were generated by nuclear star formation or by quasar-like outbursts of the central black hole and no information on the structures' magnetic field has been reported. Here we report observations of two giant, linearly polarized radio lobes, containing three ridge-like substructures, emanating from the Galactic Centre. The lobes each extend about 60 degrees in the Galactic bulge, closely corresponding to the Fermi bubbles, and are permeated by strong magnetic fields of up to 15 microgauss. We conclude that the radio lobes originate in a biconical, star-formation-driven (rather than black-hole-driven) outflow from the Galaxy's central 200 parsecs that transports a huge amount of magnetic energy, about 10(55) ergs, into the Galactic halo. The ridges wind around this outflow and, we suggest, constitute a 'phonographic' record of nuclear star formation activity over at least ten million years.

Background: Gout is the commonest inflammatory arthritis affecting around 1.4% of adults in Europe. It is predominantly managed in primary care and classically affects the joints of the foot, particularly the first metatarsophalangeal joint. Gout related factors (including disease characteristics and treatment) as well as comorbid chronic disease are associated with poor Health Related Quality of Life (HRQOL) yet to date there is limited evidence concerning gout in a community setting. Existing epidemiological studies are limited by their cross-sectional design, selection of secondary care patients with atypical disease and the use of generic tools to measure HRQOL. This 3 year primary care-based prospective observational cohort study will describe the spectrum of HRQOL in community dwelling patients with gout, associated factors, predictors of poor outcome, and prevalence and incidence of foot problems in gout patients., Methods: Adults aged  ≥ 18 years diagnosed with gout or prescribed colchicine or allopurinol in the preceding 2 years will be identified through Read codes and mailed a series of self-completion postal questionnaires over a 3-year period. Consenting participants will have their general practice medical records reviewed., Discussion: This is the first prospective cohort study of HRQOL in patients with gout in primary care in the UK. The combination of survey data and medical record review will allow an in-depth understanding of factors that are associated with and lead to poor HRQOL and foot problems in gout. Identification of these factors will improve the management of this prevalent, yet under-treated, condition in primary care.

Nursing education in the UK has lagged behind most of the developed world since inception of Project 2000 because in England, a diploma has been accepted as the basis for education, unlike other countries (including Scotland and Wales) a degree has been the accepted standard for many years. While Australia's nursing education has been more protected, an anti-intellectualism is creeping in with a technical college now offering a nursing degree, and some universities lowering their admission standards for nursing courses. Changes in the UK being imposed through the influence of the global financial crisis threaten nursing even further and this is not helped by short sighted media reports of problems with nursing care in the National Health Service. This paper examines the continuing devaluing of critical thinking, something that we contend, with the strongest emphasis, should be at the core of every aspect of nursing practice, education and research., and implications for nursing in both the UK and Australia., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Polymyalgia Rheumatica (PMR) is the commonest inflammatory condition seen in older patients in primary care. To date, however, research has been focused on secondary care cohorts rather than primary care where many patients are exclusively managed. This two year prospective inception cohort study of PMR patients will enable us to understand the full spectrum of this condition., Methods: Patients diagnosed with PMR in primary care will be identified via Read codes and mailed a series of postal questionnaires over a two-year period to assess their levels of pain, stiffness and functioning, as well as medication usage and other health-related and socio-demographic characteristics. In addition, participants will be asked for permission to link their survey data to their general practice electronic medical record and to national mortality and cancer registers., Discussion: This will be the first large-scale, prospective, observational cohort of PMR patients in primary care. The combination of survey data with medical records and national registers will allow for a full investigation of the natural history and prognosis of this condition in the primary care setting, in which the majority of patients are treated, but where little research on the treatment and outcome of consultation has been undertaken. This will provide information that may lead to improved primary care management of PMR.

Almost all locomotor animals are sensitive to optical expansion (visual looming) and for most animals this sensitivity is evident very early in their development. In humans there is evidence that responses to looming stimuli begin in the first 6 weeks of life, but here we demonstrate that as children become independent their perceptual acuity needs to be 50 to 100 times better than has been demonstrated in infants in order to be skilful at collision avoidance at a roadside. We have recently established that sensitivity to the detection of visual looming in 6- to 11-year-old children is significantly below that of adults (Wann, Poulter & Purcell, 2011). Here, using comparable methods, we explore looming detection sensitivity in children with Developmental Co-ordination Disorder (DCD), who show broad patterns of impairment in visuo-motor control. We presented visual simulations of approaching vehicles, scaled to represent different approach rates, to children with DCD aged between 6 and 11 years (n = 11) and typically developing age and gender matched controls (n = 11). Looming detection thresholds were measured under foveal and perifoveal viewing conditions, for isotropic expansion and isotropic expansion with simulated viewpoint motion. Our results show that there are situations in which children with DCD may fail to detect vehicles approaching at speeds in excess of 22 km/h, suggesting a developmental immaturity in looming sensitivity. This provides one of the first clear demonstrations of low-level motion processing deficits in children with DCD. The decrement observed may give rise to potential errors in the road crossing behaviour of these children, whereby approaching vehicles could be perceived as stationary. These findings further contribute towards understanding the adverse statistic that children under 9 years of age are four times more likely than adults to be involved in a road accident as a pedestrian., (© 2012 Blackwell Publishing Ltd.)

Next generation, foot-and-mouth disease (FMD) molecular vaccines based on replication deficient human adenovirus serotype 5 viral vectored delivery of FMD capsid genes (AdFMD) are being developed by the United States Dept. of Homeland Security and industry partners. The strategic goal of this program is to develop AdFMD licensed vaccines for the USA National Veterinary Stockpile for use, if needed, as emergency response tools during an FMD outbreak. This vaccine platform provides a unique opportunity to develop a set of in vitro analytical parameters to generate an AdFMD vaccine product profile to replace the current lot release test for traditional, inactivated FMD vaccines that requires FMDV challenge in livestock. The possibility of an indirect FMD vaccine potency test based on a serological alternative was initially investigated for a lead vaccine candidate, Adt.A24. Results show that serum virus neutralization (SVN) based serology testing for Adt.A24 vaccine lot release is not feasible, at least not in the context of vaccine potency assessment at one week post-vaccination. Thus, an in vitro infectious titer assay (tissue culture infectious dose 50, TCID50) which measures FMD infectious (protein expression) titer was established. Pre-validation results show acceptable assay variability and linearity and these data support further studies to validate the TCID50 assay as a potential potency release test. In addition, a quantitative physiochemical assay (HPLC) and three immunochemical assays (Fluorescent Focus-Forming Unit (FFU); tissue culture expression dose 50 (TCED50); Western blot) were developed for potential use as in vitro assays to monitor AdFMD vaccine lot-to-lot consistency and other potential applications. These results demonstrate the feasibility of using a traditional modified-live vaccine virus infectivity assay in combination with a set of physiochemical and immunochemical tests to build a vaccine product profile that will ensure the each AdFMD vaccine lot released is similar to a reference vaccine of proven clinical safety and efficacy.

As pedestrians, the perceptual ability to accurately judge the relative rate of approaching vehicles and select a suitable crossing gap requires sensitivity to looming. It also requires that crossing judgments are synchronized with motoric capabilities. Previous research has suggested that children with Developmental Co-ordination Disorder (DCD) may have deficits in visual processing, specifically in detecting visual motion. It is possible, therefore that this population are at greater risk at the roadside. In a series of motion prediction tasks, several component roadside skills were assessed in 15 children with DCD, or at risk of DCD, aged between 6 and 11 years along with 15 typically developing age and gender matched controls. First, threshold errors for relative approach rate judgments (looming) were measured when vehicle size (car or truck) varied. Second, thresholds for crossing gap selection were measured for vehicle approach speeds of 32, 48, 64 and 80 km/h (20-50 mph). These were related to the walking speeds of children of different ages and profiles. We found that children with DCD showed a deficit in making relative approach rate judgments, using looming, which suggests they may not discern that a vehicle is travelling faster than the urban speed limit. Children with DCD also left considerably longer temporal crossing gaps than controls perhaps reflecting a lack of confidence in their ability, these preferred gaps were over twice the average inter-car gaps that occurred on roads around their school. Our findings raise a number of issues concerning children with DCD and their competence and potential limitations as pedestrians., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Almost all locomotor animals respond to visual looming or to discrete changes in optical size. The need to detect and process looming remains critically important for humans in everyday life. Road traffic statistics confirm that children up to 15 years old are overrepresented in pedestrian casualties. We demonstrate that, for a given pedestrian crossing time, vehicles traveling faster loom less than slower vehicles, which creates a dangerous illusion in which faster vehicles may be perceived as not approaching. Our results from perceptual tests of looming thresholds show strong developmental trends in sensitivity, such that children may not be able to detect vehicles approaching at speeds in excess of 20 mph. This creates a risk of injudicious road crossing in urban settings when traffic speeds are higher than 20 mph. The risk is exacerbated because vehicles moving faster than this speed are more likely to result in pedestrian fatalities.

Background: The CXC-chemokine expression is linked with colorectal cancer (CRC) progression but their significance in resected CRC is unclear. We explored the prognostic impact of such expression in stage II and III CRC., Methods: Tissue microarrays were constructed from stage II and III CRC biopsies (n=254), and the expression of CXCL1 and CXCL8, and their receptors CXCR1 and CXCR2, in malignant and adjacent normal tissue was graded by immunohistochemistry and was correlated with prognostic factors., Results: Expression of CXCL1, CXCR1 and CXCR2 was elevated in tumour epithelium relative to normal adjacent tissue (P<0.001). CXCL8 expression was detectable in the peritumoural inflammatory infiltrate. There was no overall association between CXCL1, CXCR1 or CXCR2 expression and prognostic endpoints; however, univariate subgroup survival analysis demonstrated an inverse association between CXCL1 and recurrence-free survival (RFS) in stage III patients (P=0.041). The CXCL8 positivity in the tumour infiltrate, however, correlated with earlier disease stage (P<0.001) and improved relapse-free survival across the cohort (P<0.001). Disease stage (P<0.001) and tumour infiltrate CXCL8 positivity (P=0.007) were associated with enhanced RFS in multivariate Cox regression analysis., Conclusion: Autocrine CXC-chemokine signalling may have adverse prognostic effects in early CRC. Conversely, CXCL8 positivity within the immune infiltrate may have good prognostic significance.

Constitutive activation of nuclear factor (NF)-kappaB is linked with the intrinsic resistance of androgen-independent prostate cancer (AIPC) to cytotoxic chemotherapy. Interleukin-8 (CXCL8) is a transcriptional target of NF-kappaB whose expression is elevated in AIPC. This study sought to determine the significance of CXCL8 signaling in regulating the response of AIPC cells to oxaliplatin, a drug whose activity is reportedly sensitive to NF-kappaB activity. Administration of oxaliplatin to PC3 and DU145 cells increased NF-kappaB activity, promoting antiapoptotic gene transcription. In addition, oxaliplatin increased the transcription and secretion of CXCL8 and the related CXC-chemokine CXCL1 and increased the transcription and expression of CXC-chemokine receptors, especially CXC-chemokine receptor (CXCR) 2, which transduces the biological effects of CXCL8 and CXCL1. Stimulation of AIPC cells with CXCL8 potentiated NF-kappaB activation in AIPC cells, increasing the transcription and expression of NF-kappaB-regulated antiapoptotic genes of the Bcl-2 and IAP families. Coadministration of a CXCR2-selective antagonist, AZ10397767 (Bioorg Med Chem Lett 18:798-803, 2008), attenuated oxaliplatin-induced NF-kappaB activation, increased oxaliplatin cytotoxicity, and potentiated oxaliplatin-induced apoptosis in AIPC cells. Pharmacological inhibition of NF-kappaBorRNA interference-mediated suppression of Bcl-2 and survivin was also shown to sensitize AIPC cells to oxaliplatin. Our results further support NF-kappaB activity as an important determinant of cancer cell sensitivity to oxaliplatin and identify the induction of autocrine CXCR2 signaling as a novel mode of resistance to this drug.

Little is known about nursing students' information literacy skills and perceptions of Web-enhanced educational approaches. This study examined graduating Bachelor of Nursing (BN) students' perceptions of a Web-enhanced learning environment, their computer literacy skills, and use of technology, and how these influenced their satisfaction. This Australian survey produced a 64% (n = 170) response rate. The 3-year BN program provides Web-enhanced learning opportunities by incorporating online activities and content such as quizzes, videos, and virtual laboratories that augment on-campus and off-campus learning approaches. Upon graduation, 61.4% of the students reported having competent information literacy skills. The quality and usefulness of the Web-enhanced material was rated fair to above average. The students' perception of technical and faculty support for Web-enhanced learning was low. Overall satisfaction with the Web-enhanced program was associated with level of information technology (IT) skills and perceived quality and usefulness of the Internet material. A regression analysis of factors contributing to students' overall satisfaction of a Web-enhanced learning environment (IT literacy skills, access, and perceived quality, usefulness, and support) accounted for 18.5% of variance. As more nursing programs use Web-based resources, greater attention should be given to the initial assessment and development of students' information literacy skills. Students with good IT skills are more likely to perceive Web-enhanced material as useful.

We have shown previously that interleukin-8 (IL-8) and IL-8 receptor expression is elevated in tumor cells of human prostate biopsy tissue and correlates with increased cyclin D1 expression. Using PC3 and DU145 cell lines, we sought to determine whether IL-8 signaling regulated cyclin D1 expression in androgen-independent prostate cancer (AIPC) cells and to characterize the signaling pathways underpinning this response and that of IL-8-promoted proliferation. Administration of recombinant human IL-8 induced a rapid, time-dependent increase in cyclin D1 expression in AIPC cells, a response attenuated by the translation inhibitor cycloheximide but not by the RNA synthesis inhibitor, actinomycin D. Suppression of endogenous IL-8 signaling using neutralizing antibodies to IL-8 or its receptors also attenuated basal cyclin D1 expression in AIPC cells. Immunoblotting using phospho-specific antibodies confirmed that recombinant human IL-8 induced rapid time-dependent phosphorylation of Akt and the mammalian target of rapamycin substrate proteins, 4E-BP1 and ribosomal S6 kinase, resulting in a downstream phosphorylation of the ribosomal S6 protein (rS6). LY294002 and rapamycin each abrogated the IL-8-promoted phosphorylation of rS6 and attenuated the rate of AIPC cell proliferation. Our results indicate that IL-8 signaling (a) regulates cyclin D1 expression at the level of translation, (b) regulates the activation of proteins associated with the translation of capped and 5'-oligopyrimidine tract transcripts, and (c) activates signal transduction pathways underpinning AIPC cell proliferation. This study provides a molecular basis to support the correlation of IL-8 expression with that of cyclin D1 in human prostate cancer and suggests a mechanism by which this chemokine promotes cell proliferation.

So-called diseases of affluence, otherwise known as 'lifestyle diseases', are attributed to modifiable risk factors that are influenced by lifestyle and personal behaviour. Leading by example is an important way for public health principles to be communicated. In the university context, students of nursing can become aware of the challenge to integrate and apply health principles in their own life so that they become responsible health leaders in the community. The aim of this study was to explore the incidence of a number of behaviour-associated health risk factors within a group of undergraduate nursing students. Ninety-four students participated in the study. Seventy-seven students (82%) reported the presence of at least one modifiable health risk factor. Forty-four percent of respondents were either overweight or obese. Further research to explore whether a health promoting curriculum encourages nursing students to internalise/apply health knowledge to their own lives is recommended. A campaign of public health might be useful within the university community to educate students about risk factors and healthy living.

The human voluntary force:velocity relationship frequently fails to demonstrate the expected high eccentric forces. Possible explanations include unique activation strategies which might be affected by neural learning mechanisms. We investigated the effect of practicing eccentric contractions on (1) the force:velocity relationship of the human knee extensor muscles and (2) the extent of agonist and antagonist muscle activity. Eight healthy adults [seven women, group mean age 31 (SEM 5) years +/-] practiced twice a week for 4 weeks using their non-dominant legs. Each session comprised three isokinetic concentric and eccentric maximal voluntary contractions (MVC) at randomised angular velocities of 100, 200 and 300 degrees.s-1. Before and after, the force:velocity relationship was determined bilaterally (angular velocities 0-300 degrees.s-1). There were no significant differences in the forces generated or relative electromyogram (EMG) activity after practice, although there was a trend for dynamic forces to increase. Beforehand, the bilateral eccentric MVC forces were lower than isometric (P < 0.0025); afterwards they were broadly similar. The agonist EMG was similar during isometric and eccentric contractions, but lower during concentric (P < 0.03). Antagonist EMG activity showed considerable individual variation, was similar during all contraction types and tended to be greater during dynamic contractions. These data indicate that neither central learning mechanisms nor total muscle activation strategies underlie the human failure to produce the expected high eccentric voluntary forces in humans.

Autologous vein grafts are employed extensively to bypass stenoses in the arterial circulation. More recently arterial segments have been used for such bypass surgery. In this study the adaptation of regenerating vascular tissues in experimental autologous artery grafts (4 mm long and 1 mm in diameter) in 20 adult male Wistar rats was analysed. At 1, 2, 4, 8 and 16 wk after insertion, 4 grafts per time interval were removed, processed for high resolution light microscopy and the thicknesses of the media and neointima, as well as the area fractions of smooth muscle cells, were analysed morphometrically. All grafts were reendothelialised by 2 wk. Neointimal hyperplasia (a subendothelial layer of smooth muscle cells) developed in all grafts and reached its maximal thickness (40.4 +/- 4.7 microns) at 2 wk. The area fraction of smooth muscle cells in the neointima of the artery grafts did not change significantly at any time from 2 to 16 wk. The media underlying the neointima of the artery grafts remained relatively constant throughout the 16 wk duration of the experiment. Whilst the total wall thickness of the grafts reduced significantly between 2 and 4 wk after insertion, at all times the grafts were thicker than the host artery.

With the advent of modern microsurgical procedures and an improved understanding of the cellular dynamics of vascular graft adaptation, arterial grafts are being used more frequently in surgical practice. In this article the structure and development of neointimal hyperplasia in vascular grafts, both venous and arterial, are reviewed briefly. The underlying biology of venous graft adaptation is now well understood. However, in addition to venous grafts, many different arterial conduits are now being used; these include the radial artery, internal mammary (thoracic) and gastroepiploic arteries. The different clinical outcomes of these arterial grafts and the underlying cell biology of their adaptation to the grafted environment are also reviewed.

In this paper the ethical and legal implications of withdrawing treatment from a critically-ill child are examined. Paediatric nurses in intensive care units often rely on intuition for resolving emotive issues such as the withdrawal of treatment from a child. To enhance their contribution in the decision-making process nurses need knowledge of ethical theories and principles, and the law. Advances in technology, together with political and economic factors, could well result in more attention being placed on ethical and legal issues in paediatric intensive care units. For the purpose of this paper pseudonyms have been used.

The preparation of school-age children and their parents for intensive care following cardiac surgery for congenital heart disease merits discussion. The prospect of cardiac surgery and the ensuing admission to an intensive care unit can pose many real and imagined threats and can be extremely stressful for both children and their parents. The focus in this paper is on methods of preparation, aspects of hospitalisation and intensive care that children and their parents find stressful and how preparation can help to alleviate this stress.

Objective: To investigate the effects of chronic calcium pyrophosphate dihydrate (CPPD) synovitis on the development of osteoarthritic (OA) lesions in an animal model., Methods: OA was induced in the right knees of 30 male New Zealand white rabbits by partial lateral meniscectomy and section of the fibular collateral and sesamoid ligaments (PLM/LS), followed by 8 weekly intraarticular (IA) injections of 1 mg (low-dose) or 10 mg (high-dose) of CPPD crystals in 3 sets of experiments (10 rabbits each). The contralateral left knees served as controls: experiment 1 PLM/LS alone, experiment 2 8 weekly IA injections of CPPD crystals alone, and experiment 3 sham surgery plus 8 weekly IA injections of CPPD crystals., Results: At 8 weeks, repeated IA injections of low-dose and high-dose CPPD crystals into meniscectomized right knees resulted in more severe OA than in meniscectomized but noninjected left knees (experiment 1) (P = 0.003 and P = 0.001, respectively). One-fourth of the meniscectomized knees (11 of 40), both CPPD-injected and noninjected, showed embedded synovial cartilage shards., Conclusion: The data demonstrate a worsening effect of chronic CPPD crystal-induced synovitis on experimental OA produced in the rabbit knees by PLM/LS, and support a possible role for CPPD microcrystalline inflammation in the progression of OA lesions in clinical CPPD crystal deposition disease.

This paper describes two different models of nursing that have been used to care for children in hospital, emphasising how such care is planned and delivered. Although it began as an academic exercise, it is hoped that in using the ideas contained in it nurses involved in the care of critically ill children could begin to look at alternative methods of planning and delivering holistic care. In particular it is suggested that more traditional methods of care planning may not always provide enough reference to the important psychosocial and developmental needs of each child in an intensive care unit (ICU).

Sleep disordered breathing (SDB) may be associated with cognitive dysfunction in non-demented elderly people. A random sample of 96 retirement village residents were given both neuropsychological assessment and overnight sleep monitoring with a portable microprocessor based system (Vitalog PMS-8). Respiratory disturbance index (RDI) was calculated as the number of apnoeas and hypopnoeas per hour of sleep. RDI was not associated with 'memory', 'verbal', and 'motor' factors identified from the analysis of cognitive tests, but was associated with the 'cerebral efficiency' factor (R2 = 0.21, p less than 0.0001). Seventy-three subjects had repeat neuropsychological tests, median time to follow-up being 17 months. Baseline RDI did not predict changes in scores on the two factors identified from the second analysis. We conclude that mild to moderate disturbance of breathing during sleep is not associated with cognitive dysfunction in non-demented subjects.

Blood loss, survival, and hemodynamics were monitored for 1 hour or until death in 30 anesthetized pigs with a 0.5 cm abdominal aortic laceration. Eight animals (Group I) had no treatment; 7 animals (Group IA) had saline infusion at a maximum rate of 200 mls/min to maintain carotid artery pressure (CP); 8 animals (Group II) had intraabdominal pressure increased to 60 torr by pneumatic antishock garment (PASG) inflation; and 7 animals (Group IIA) had PASG inflation with saline infusion to maintain CP. Groups I and IA survived 9.5 +/- 4.2 minutes and 28.0 +/- 5.5 minutes, respectively (p less than 0.05). Groups II and IIA survived the 1 hour. Saline infusion (5400 +/- 120 mls in Group IA and 535 +/- 180 mls in Group IIA, p less than 0.05) increased blood loss without PASG inflation (1289 +/- 49 mls in Group I vs. 4840 +/- 1350 mls in Group IA, p less than 0.05) as well as with PASG inflation (438 +/- 64 mls in Group II vs. 1235 +/- 68 mls in Group IIA, p less than 0.05). CP could not be maintained in spite of saline infusion in Group IA but in Group IIA CP was maintained with saline infusion. In an otherwise fatal abdominal aortic laceration, increasing intraabdominal pressure improves survival and decreases hemorrhage. While saline infusion may prolong survival it increases hemorrhage both in the presence and absence of increased intraabdominal pressure.

To determine if the increased blood pressure associated with application of a pneumatic antishock garment (PASG) affects outcome in thoracic hemorrhage, we assessed hemodynamics, blood loss, and survival in three groups of eight anaesthetized piglets with a 2.5-mm laceration of the descending thoracic aorta. Baseline measurements were made before aortic hemorrhage. During one hour of aortic hemorrhage or until death of the animal, the PASG was not inflated in Group I while the PASG in the other two groups was inflated to maintain carotid artery pressure at 15 torr below baseline (Group II) and at baseline (Group III), respectively. Survival was 100% in Group I, 50% in Group II, and 0% in Group III. Hemorrhage at 22.5 +/- 4.0 mL/min stopped after 18-24 minutes in Group I; the survivors in Group II bled at a rate of 32.5 +/- 3.0 mL/min compared with 43.6 +/- 4.0 mL/min over 26-35 minutes in the Group II nonsurvivors. Group III pigs bled at 107.5 +/- 8.0 mL/min over the 10-18 minutes of survival. The intended blood pressure could not be maintained beyond 30 minutes. Bleeding stopped in Group I when the blood pressure fell to 58.2 +/- 4.5 torr from a baseline of 119.0 +/- 10.0 torr. The blood pressure fell to 48.0 +/- 5.0 torr in the four Group-II survivors. After a transient maintenance of baseline blood pressure in Group III, a precipitous drop in blood pressure with death in 10-18 minutes occurred in all these animals. In this porcine model of thoracic aortic injury, PASG inflation increases hemorrhage and mortality.(ABSTRACT TRUNCATED AT 250 WORDS)

Surface harmonic expansions are used to represent boundaries between regions of different conductivity in the human head. This facilitates calculation of the electric potential and magnetic field generated by neural current sources using discretized integral equations.

The accuracy with which electrical sources in the brain can be localized by using electroencephalograms measured on the scalp is not well known. In this study, tests of localization accuracy were performed by using implanted dipolar sources in the human brain. These dipoles are created by passing a weak (subthreshold) current through intracerebral electrodes implanted in the brains of epileptic patients for seizure monitoring. The locations of these dipoles are accurately known from roentgenographs. First, 16 electroencephalograms produced by these dipoles were recorded, then inverse solutions were calculated for the apparent sources of these electroencephalograms. Finally, the locations of the apparent sources were compared with the known locations of the implanted dipoles to determine localization error. The average localization error for a total of 28 dipoles in 3 subjects was 1.1 cm. These results indicate that good localization accuracy for focal sources in the brain can be provided by scalp electroencephalograms.

In our magnetocardiographic (MCG) localisation studies, two modelling approaches have been applied: (a) modelling the sources with dipole and quadrupole moments in a general multipole expansion and using a homogeneous, semi-infinite volume conductor, and (b) using a single current dipole source in a homogeneous, realistically shaped torso. Both approaches have been successfully applied in localising the premature ventricular excitation site in patients suffering from the Wolff-Parkinson-White syndrome. In addition, we have participated in developing a model of propagation of electrical activation in the ventricles. Anisotropic conductivity properties and spiral arrangement of myocardial fibres are included in the model.

It is believed that the magnetoencephalogram (MEG) localizes an electrical source in the brain to within several millimeters and is therefore more accurate than electroencephalogram (EEG) localization, reported as 20 mm. To test this belief, the localization accuracy of the MEG and EEG were directly compared. The signal source was a dipole at a known location in the brain; this was made by passing a weak current pulse simulating a neural signal through depth electrodes already implanted in patients for seizure monitoring. First, MEGs and EEGs from this dipole were measured at 16 places on the head. Then, computations were performed on the MEG and EEG data separately to determine the apparent MEG and EEG source locations. Finally, these were compared with the actual source location to determine the MEG and EEG localization errors. Measurements were made of four dipoles in each of three patients. After MEGs with weak signals were discounted, the MEG average error of localization was found to be 8 mm, which was worse than expected. The average EEG error was 10 mm, which was better than expected. These results suggest that the MEG offers no significant advantage over the EEG in localizing a focal source. However, this does not diminish other uses of the MEG.

Our study confirms that multiple medications are frequently taken by relatively healthy residents of a retirement village, the more so when they are less socially active during the day, and when they are living in hostel accommodation. There were few drug combinations that caused a potential interaction, suggesting that safe use of medication by the elderly should be an achievable goal.