'They're battle scars, I wear them well': A phenomenological exploration of young women's experiences of building resilience following adversity in adolescence

This is an Author's Accepted Manuscript of an article published in Journal of Youth Studies, 13(3), 273 - 290, 2010 [copyright Taylor & Francis], available online at: http://www.tandfonline.com/10.1080/13676260903520886.This phenomenological study explored young women's accounts of building resilience following chains of adverse life experiences in adolescence. Six participants were interviewed, aged 20–25 years. Most had, or were receiving, a university education. They described their recovery from adversity as starting with certain pivotal moments, followed by both short-term and longer-term strategies. Short-term strategies tended to offer respite from distress and emotional comfort, increased clarity about their experiences and social affirmation. Recovery involved gaining new perspectives on their adverse situation and recovering a positive self-image through three longer-term strategies. These involved making visible progress in their education, rebuilding relationships with family and friends, and participating in the ‘normalizing’ activities and developmental projects of adolescence. Participants believed that they were stronger and more compassionate although positive achievements co-existed with some regrets. Most perceived the adversity as catalyzing personal growth. These accounts of resilience revealed the complex psychosocial processes and resources available to some adolescents

Analysis of immune responses to attenuated alcelaphine herpesvirus 1 formulated with and without adjuvant

The experimental vaccine for bovine malignant catarrhal fever consists of viable attenuated alcelaphine herpesvirus 1 (AlHV-1) derived by extensive culture passage, combined with an oil-in-water adjuvant, delivered intramuscularly. This immunisation strategy was over 80% effective in previous experimental and field trials and protection appeared to be associated with induction of virus-neutralising antibodies. Whether the vaccine virus is required to be viable at the point of immunisation and whether adjuvant is required to induce the appropriate immune responses remains unclear. To address these issues two studies were performed, firstly to analyse immune responses in the presence and absence of adjuvant and secondly, to investigate immune responses to vaccines containing adjuvant plus viable or inactivated AlHV-1.The first study showed that viable attenuated AlHV-1 in the absence of adjuvant induced virus-specific antibodies but the titres of virus-neutralising antibodies were significantly lower than those induced by vaccine containing viable virus and adjuvant, suggesting adjuvant was required for optimal responses. In contrast, the second study found that the vaccine containing inactivated (>99.9%) AlHV-1 induced similar levels of virus-neutralising antibody to the equivalent formulation containing viable AlHV-1.Together these studies suggest that the MCF vaccine acts as an antigen depot for induction of immune responses, requiring adjuvant and a suitable antigen source, which need not be viable virus. These observations may help in directing the development of alternative MCF vaccine formulations for distribution in the absence of an extensive cold chain

Challenging Perceptions of Disability through Performance Poetry Methods: The "Seen but Seldom Heard" Project.

This paper considers performance poetry as a method to explore lived experiences of disability. We discuss how poetic inquiry used within a participatory arts-based research framework can enable young people to collectively question society’s attitudes and actions towards disability. Poetry will be considered as a means to develop a more accessible and effective arena in which young people with direct experience of disability can be empowered to develop new skills that enable them to tell their own stories. Discussion of how this can challenge audiences to critically reflect upon their own perceptions of disability will also be developed

Weight loss referrals for adults in primary care (WRAP) : Protocol for a multi-centre randomised controlled trial comparing the clinical and cost-effectiveness of primary care referral to a commercial weight loss provider for 12 weeks, referral for 52 weeks, and a brief self-help intervention [ISRCTN82857232]

Background: Recent trials demonstrate the acceptability and short term efficacy of primary care referral to a commercial weight loss provider for weight management. Commissioners now need information on the optimal duration of intervention and the longer term outcomes and cost effectiveness of such treatment to give best value for money. Methods/Design. This multicentre, randomised controlled trial with a parallel design will recruit 1200 overweight adults (BMI ≥28 kg/m2) through their primary care provider. They will be randomised in a 2:5:5 allocation to: Brief Intervention, Commercial Programme for 12 weeks, or Commercial Programme for 52 weeks. Participants will be followed up for two years, with assessments at 0, 3, 12 and 24 months. The sequential primary research questions are whether the CP interventions achieve significantly greater weight loss from baseline to 12 months than BI, and whether CP52 achieves significantly greater weight loss from baseline to 12 months than CP12. The primary outcomes will be an intention to treat analysis of between treatment differences in body weight at 12 months. Clinical effectiveness will be also be assessed by measures of weight, fat mass, and blood pressure at each time point and biochemical risk factors at 12 months. Self-report questionnaires will collect data on psychosocial factors associated with adherence, weight-loss and weight-loss maintenance. A within-trial and long-term cost-effectiveness analysis will be conducted from an NHS perspective. Qualitative methods will be used to examine the participant experience. Discussion. The current trial compares the clinical and cost effectiveness of referral to a commercial provider with a brief intervention. This trial will specifically examine whether providing longer weight-loss treatment without altering content or intensity (12 months commercial referral vs. 12 weeks) leads to greater weight loss at one year and is sustained at 2 years. It will also evaluate the relative cost-effectiveness of the three interventions. This study has direct implications for primary care practice in the UK and will provide important information to inform the decisions of practitioners and commissioners about service provision

Association of CD40 with rheumatoid arthritis confirmed in a large UK case-control study

OBJECTIVE: A recent meta-analysis of published genome-wide association studies (GWAS) in populations of European descent reported novel associations of markers mapping to the CD40, CCL21 and CDK6 genes with rheumatoid arthritis (RA) susceptibility while a large-scale, case-control association study in a Japanese population identified association with multiple single nucleotide polymorphisms (SNPs) in the CD244 gene. The aim of the current study was to validate these potential RA susceptibility markers in a UK population. METHODS: A total of 4 SNPs (rs4810485 in CD40, rs2812378 in CCL21, rs42041 in CDK6 and rs6682654 in CD244) were genotyped in a UK cohort comprising 3962 UK patients with RA and 3531 healthy controls using the Sequenom iPlex platform. Genotype counts in patients and controls were analysed with the chi(2) test using Stata. RESULTS: Association to the CD40 gene was robustly replicated (p=2 x 10(-4), OR 0.86, 95% CI 0.79 to 0.93) and modest evidence was found for association with the CCL21 locus (p=0.04, OR 1.08, 95% CI 1.01 to 1.16). However, there was no evidence for association of rs42041 (CDK6) and rs6682654 (CD244) with RA susceptibility in this UK population. Following a meta-analysis including the original data, association to CD40 was confirmed (p=7.8 x 10(-8), OR 0.87 (95% CI 0.83 to 0.92). CONCLUSION: In this large UK cohort, strong association of the CD40 gene with susceptibility to RA was found, and weaker evidence for association with RA in the CCL21 locus

PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population

BACKGROUND: Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the PADI4 genotype with RA in a large UK Caucasian population. METHODS: The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study. RESULTS: The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12). CONCLUSION: In the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations

Fluid Optimisation in Emergency Laparotomy (FLO-ELA) Trial: study protocol for a multi-centre randomised trial of cardiac output-guided fluid therapy compared to usual care in patients undergoing major emergency gastrointestinal surgery

INTRODUCTION: Postoperative morbidity and mortality in patients undergoing major emergency gastrointestinal surgery are a major burden on healthcare systems. Optimal management of perioperative intravenous fluids may reduce mortality rates and improve outcomes from surgery. Previous small trials of cardiac-output guided haemodynamic therapy algorithms in patients undergoing gastrointestinal surgery have suggested this intervention results in reduced complications and a modest reduction in mortality. However, this existing evidence is based mainly on elective (planned) surgery, with little evaluation in the emergency setting. There are fundamental clinical and pathophysiological differences between the planned and emergency surgical setting which may influence the effects of this intervention. A large definitive trial in emergency surgery is needed to confirm or refute the potential benefits observed in elective surgery and to inform widespread clinical practice. METHODS: The FLO-ELA trial is a multi-centre, parallel-group, open, randomised controlled trial. 3138 patients aged 50 and over undergoing major emergency gastrointestinal surgery will be randomly allocated in a 1:1 ratio using minimisation to minimally invasive cardiac output monitoring to guide protocolised administration of intra-venous fluid, or usual care without cardiac output monitoring. The trial intervention will be carried out during surgery and for up to 6 h postoperatively. The trial is funded through an efficient design call by the National Institute for Health and Care Research Health Technology Assessment (NIHR HTA) programme and uses existing routinely collected datasets for the majority of data collection. The primary outcome is the number of days alive and out of hospital within 90 days of randomisation. Participants and those delivering the intervention will not be blinded to treatment allocation. Participant recruitment started in September 2017 with a 1-year internal pilot phase and is ongoing at the time of publication. DISCUSSION: This will be the largest contemporary randomised trial examining the effectiveness of perioperative cardiac output-guided haemodynamic therapy in patients undergoing major emergency gastrointestinal surgery. The multi-centre design and broad inclusion criteria support the external validity of the trial. Although the clinical teams delivering the trial interventions will not be blinded, significant trial outcome measures are objective and not subject to detection bias. TRIAL REGISTRATION: ISRCTN 14729158. Registered on 02 May 2017

A comparison of particle mass spectrometers during the 1999 Atlanta Supersite Project

During the Atlanta Supersite Project, four particle mass spectrometers were operated together for the first time: NOAA's Particle Analysis by Laser Mass Spectrometer (PALMS), University of California at Riverside's Aerosol Time-of-Flight Mass Spectrometer (ATOFMS), University of Delaware's Rapid Single-Particle Mass Spectrometer II (RSMS-II), and Aerodyne's Aerosol Mass Spectrometer (AMS). Although these mass spectrometers are generally classified as similar instruments, they clearly have different characteristics due to their unique designs. One primary difference is related to the volatilization/ionization method: PALMS, ATOFMS, and RSMS-II utilize laser desorption/ionization, whereas particles in the AMS instrument are volatilized by impaction onto a heated surface with the resulting components ionized by electron impact. Thus mass spectral data from the AMS are representative of the ensemble of particles sampled, and those from the laser-based instruments are representative of individual particles. In addition, the AMS instrument cannot analyze refractory material such as soot, sodium chloride, and crustal elements, and some sulfate or water-rich particles may not always be analyzed with every laser-based instrument. A main difference among the laser-based mass spectrometers is that the RSMS-II instrument can obtain size-resolved single particle composition information for particles with aerodynamic diameters as small as 15 nm. The minimum sizes analyzed by ATOFMS and PALMS are 0.2 and about 0.35 μm, respectively, in aerodynamic diameter. Furthermore, PALMS, ATOFMS, and RSMS-II use different laser ionization conditions. Despite these differences the laser-based instruments found similar individual particle classifications, and their relative fractions among comparable sized particles from Atlanta were broadly consistent. Finally, the AMS measurements of the nitrate/sulfate mole ratio were highly correlated with composite measurements (r^2 = 0.93). In contrast, the PALMS nitrate/sulfate ion ratios were only moderately correlated (r^2 ∼ 0.7)

Overlapping genetic susceptibility variants between three autoimmune disorders: rheumatoid arthritis, type 1 diabetes and coeliac disease

INTRODUCTION: Genome wide association studies, replicated by numerous well powered validation studies, have revealed a large number of loci likely to play a role in susceptibility to many multifactorial diseases. It is now well established that some of these loci are shared between diseases with similar aetiology. For example, a number of autoimmune diseases have been associated with variants in the PTPN22, TNFAIP3 and CTLA4 genes. Here we have attempted to define overlapping genetic variants between rheumatoid arthritis (RA), type 1 diabetes (T1D) and coeliac disease (CeD). METHODS: We selected eight SNPs previously identified as being associated with CeD and six T1D-associated SNPs for validation in a sample of 3,962 RA patients and 3,531 controls. Genotyping was performed using the Sequenom MassArray platform and comparison of genotype and allele frequencies between cases and controls was undertaken. A trend test P-value < 0.004 was regarded as significant. RESULTS: We found statistically significant evidence for association of the TAGAP locus with RA (P = 5.0 × 10-4). A marker at one other locus, C1QTNF6, previously associated with T1D, showed nominal association with RA in the current study but did not remain statistically significant at the corrected threshold. CONCLUSIONS: In exploring the overlap between T1D, CeD and RA, there is strong evidence that variation within the TAGAP gene is associated with all three autoimmune diseases. Interestingly a number of loci appear to be specific to one of the three diseases currently studied suggesting that they may play a role in determining the particular autoimmune phenotype at presentation