Study protocol for the optimisation, feasibility testing and pilot cluster randomised trial of Positive Choices: a school-based social marketing intervention to promote sexual health, prevent unintended teenage pregnancies and address health inequalities in England.

BACKGROUND: Since the introduction of the Teenage Pregnancy Strategy (TPS), England's under-18 conception rate has fallen by 55%, but a continued focus on prevention is needed to maintain and accelerate progress. The teenage birth rate remains higher in the UK than comparable Western European countries. Previous trials indicate that school-based social marketing interventions are a promising approach to addressing teenage pregnancy and improving sexual health. Such interventions are yet to be trialled in the UK. This study aims to optimise and establish the feasibility and acceptability of one such intervention: Positive Choices. METHODS: Design: Optimisation, feasibility testing and pilot cluster randomised trial.Interventions: The Positive Choices intervention comprises a student needs survey, a student/staff led School Health Promotion Council (SHPC), a classroom curriculum for year nine students covering social and emotional skills and sex education, student-led social marketing activities, parent information and a review of school sexual health services.Systematic optimisation of Positive Choices will be carried out with the National Children's Bureau Sex Education Forum (NCB SEF), one state secondary school in England and other youth and policy stakeholders.Feasibility testing will involve the same state secondary school and will assess progression criteria to advance to the pilot cluster RCT.Pilot cluster RCT with integral process evaluation will involve six different state secondary schools (four interventions and two controls) and will assess the feasibility and utility of progressing to a full effectiveness trial.The following outcome measures will be trialled as part of the pilot:Self-reported pregnancy and unintended pregnancy (initiation of pregnancy for boys) and sexually transmitted infections,Age of sexual debut, number of sexual partners, use of contraception at first and last sex and non-volitional sexEducational attainmentThe feasibility of linking administrative data on births and termination to self-report survey data to measure our primary outcome (unintended teenage pregnancy) will also be tested. DISCUSSION: This will be the first UK-based pilot trial of a school-wide social marketing intervention to reduce unintended teenage pregnancy and improve sexual health. If this study indicates feasibility and acceptability of the optimised Positive Choices intervention in English secondary schools, plans will be initiated for a phase III trial and economic evaluation of the intervention. TRIAL REGISTRATION: ISRCTN registry (ISCTN12524938. Registered 03/07/2017)

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

A school-based social-marketing intervention to promote sexual health in English secondary schools: the Positive Choices pilot cluster RCT

Background: The UK still has the highest rate of teenage births in western Europe. Teenagers are also the age group most likely to experience unplanned pregnancy, with around half of conceptions in those aged < 18 years ending in abortion. After controlling for prior disadvantage, teenage parenthood is associated with adverse medical and social outcomes for mothers and children, and increases health inequalities. This study evaluates Positive Choices (a new intervention for secondary schools in England) and study methods to assess the value of a Phase III trial. Objectives: To optimise and feasibility-test Positive Choices and then conduct a pilot trial in the south of England assessing whether or not progression to Phase III would be justified in terms of prespecified criteria. Design: Intervention optimisation and feasibility testing; pilot randomised controlled trial. Setting: The south of England: optimisation and feasibility-testing in one secondary school; pilot cluster trial in six other secondary schools (four intervention, two control) varying by local deprivation and educational attainment. Participants: School students in year 8 at baseline, and school staff. Interventions: Schools were randomised (1 : 2) to control or intervention. The intervention comprised staff training, needs survey, school health promotion council, year 9 curriculum, student-led social marketing, parent information and review of school/local sexual health services. Main outcome measures: The prespecified criteria for progression to Phase III concerned intervention fidelity of delivery and acceptability; successful randomisation and school retention; survey response rates; and feasible linkage to routine administrative data on pregnancies. The primary health outcome of births was assessed using routine data on births and abortions, and various self-reported secondary sexual health outcomes. Data sources: The data sources were routine data on births and abortions, baseline and follow-up student surveys, interviews, audio-recordings, observations and logbooks. Results: The intervention was optimised and feasible in the first secondary school, meeting the fidelity targets other than those for curriculum delivery and criteria for progress to the pilot trial. In the pilot trial, randomisation and school retention were successful. Student response rates in the intervention group and control group were 868 (89.4%) and 298 (84.2%), respectively, at baseline, and 863 (89.0%) and 296 (82.0%), respectively, at follow-up. The target of achieving ≥ 70% fidelity of implementation of essential elements in three schools was achieved. Coverage of relationships and sex education topics was much higher in intervention schools than in control schools. The intervention was acceptable to 80% of students. Interviews with staff indicated strong acceptability. Data linkage was feasible, but there were no exact matches for births or abortions in our cohort. Measures performed well. Poor test–retest reliability on some sexual behaviour measures reflected that this was a cohort of developing adolescents. Qualitative research confirmed the appropriateness of the intervention and theory of change, but suggested some refinements. Limitations: The optimisation school underwent repeated changes in leadership, which undermined its participation. Moderator analyses were not conducted as these would be very underpowered. Conclusion: Our findings suggest that this intervention has met prespecified criteria for progression to a Phase III trial. Future work: Declining prevalence of teenage pregnancy suggests that the primary outcome in a full trial could be replaced by a more comprehensive measure of sexual health. Any future Phase III trial should have a longer lead-in from randomisation to intervention commencement

Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

Argumentation in school science : Breaking the tradition of authoritative exposition through a pedagogy that promotes discussion and reasoning

The value of argumentation in science education has become internationally recognised and has been the subject of many research studies in recent years. Successful introduction of argumentation activities in learning contexts involves extending teaching goals beyond the understanding of facts and concepts, to include an emphasis on cognitive and metacognitive processes, epistemic criteria and reasoning. The authors focus on the difficulties inherent in shifting a tradition of teaching from one dominated by authoritative exposition to one that is more dialogic, involving small-group discussion based on tasks that stimulate argumentation. The paper builds on previous research on enhancing the quality of argument in school science, to focus on how argumentation activities have been designed, with appropriate strategies, resources and modelling, for pedagogical purposes. The paper analyses design frameworks, their contexts and lesson plans, to evaluate their potential for enhancing reasoning through foregrounding the processes of argumentation. Examples of classroom dialogue where teachers adopt the frameworks/plans are analysed to show how argumentation processes are scaffolded. The analysis shows that several layers of interpretation are needed and these layers need to be aligned for successful implementation. The analysis serves to highlight the potential and limitations of the design frameworks

Non-homologous end-joining pathway associated with occurrence of myocardial infarction: gene set analysis of genome-wide association study data

&lt;p&gt;Purpose: DNA repair deficiencies have been postulated to play a role in the development and progression of cardiovascular disease (CVD). The hypothesis is that DNA damage accumulating with age may induce cell death, which promotes formation of unstable plaques. Defects in DNA repair mechanisms may therefore increase the risk of CVD events. We examined whether the joints effect of common genetic variants in 5 DNA repair pathways may influence the risk of CVD events.&lt;/p&gt; &lt;p&gt;Methods: The PLINK set-based test was used to examine the association to myocardial infarction (MI) of the DNA repair pathway in GWAS data of 866 subjects of the GENetic DEterminants of Restenosis (GENDER) study and 5,244 subjects of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. We included the main DNA repair pathways (base excision repair, nucleotide excision repair, mismatch repair, homologous recombination and non-homologous end-joining (NHEJ)) in the analysis.&lt;/p&gt; &lt;p&gt;Results: The NHEJ pathway was associated with the occurrence of MI in both GENDER (P = 0.0083) and PROSPER (P = 0.014). This association was mainly driven by genetic variation in the MRE11A gene (PGENDER = 0.0001 and PPROSPER = 0.002). The homologous recombination pathway was associated with MI in GENDER only (P = 0.011), for the other pathways no associations were observed.&lt;/p&gt; &lt;p&gt;Conclusion: This is the first study analyzing the joint effect of common genetic variation in DNA repair pathways and the risk of CVD events, demonstrating an association between the NHEJ pathway and MI in 2 different cohorts.&lt;/p&gt

A systematic review of tests of empathy in medicine

Abstract Background Empathy is frequently cited as an important attribute in physicians and some groups have expressed a desire to measure empathy either at selection for medical school or during medical (or postgraduate) training. In order to do this, a reliable and valid test of empathy is required. The purpose of this systematic review is to determine the reliability and validity of existing tests for the assessment of medical empathy. Methods A systematic review of research papers relating to the reliability and validity of tests of empathy in medical students and doctors. Journal databases (Medline, EMBASE, and PsycINFO) were searched for English-language articles relating to the assessment of empathy and related constructs in applicants to medical school, medical students, and doctors. Results From 1147 citations, we identified 50 relevant papers describing 36 different instruments of empathy measurement. As some papers assessed more than one instrument, there were 59 instrument assessments. 20 of these involved only medical students, 30 involved only practising clinicians, and three involved only medical school applicants. Four assessments involved both medical students and practising clinicians, and two studies involved both medical school applicants and students. Eight instruments demonstrated evidence of reliability, internal consistency, and validity. Of these, six were self-rated measures, one was a patient-rated measure, and one was an observer-rated measure. Conclusion A number of empathy measures available have been psychometrically assessed for research use among medical students and practising medical doctors. No empathy measures were found with sufficient evidence of predictive validity for use as selection measures for medical school. However, measures with a sufficient evidential base to support their use as tools for investigating the role of empathy in medical training and clinical care are available.</p

Drosophila S2 Cells Are Non-Permissive for Vaccinia Virus DNA Replication Following Entry via Low pH-Dependent Endocytosis and Early Transcription

Vaccinia virus (VACV), a member of the chordopox subfamily of the Poxviridae, abortively infects insect cells. We have investigated VACV infection of Drosophila S2 cells, which are useful for protein expression and genome-wide RNAi screening. Biochemical and electron microscopic analyses indicated that VACV entry into Drosophila S2 cells depended on the VACV multiprotein entry-fusion complex but appeared to occur exclusively by a low pH-dependent endocytic mechanism, in contrast to both neutral and low pH entry pathways used in mammalian cells. Deep RNA sequencing revealed that the entire VACV early transcriptome, comprising 118 open reading frames, was robustly expressed but neither intermediate nor late mRNAs were made. Nor was viral late protein synthesis or inhibition of host protein synthesis detected by pulse-labeling with radioactive amino acids. Some reduction in viral early proteins was noted by Western blotting. Nevertheless, synthesis of the multitude of early proteins needed for intermediate gene expression was demonstrated by transfection of a plasmid containing a reporter gene regulated by an intermediate promoter. In addition, expression of a reporter gene with a late promoter was achieved by cotransfection of intermediate genes encoding the late transcription factors. The requirement for transfection of DNA templates for intermediate and late gene expression indicated a defect in viral genome replication in VACV-infected S2 cells, which was confirmed by direct analysis. Furthermore, VACV-infected S2 cells did not support the replication of a transfected plasmid, which occurs in mammalian cells and is dependent on all known viral replication proteins, indicating a primary restriction of DNA synthesis

Barriers to obesity management: a pilot study of primary care clinicians

BACKGROUND: Obesity is an increasing epidemic in both the US and veteran populations, yet it remains largely understudied in the Veteran's Health Administration (VHA) setting. The purpose of our study was to identify barriers to the effective management of obesity in VHA primary care settings. METHODS: Three focus groups of clinicians from a Veteran's Affairs Medical Center (VAMC) and an affiliated Community Based Outpatient Center (CBOC) were conducted to identify potential barriers to obesity management. The focus groups and previously published studies then informed the creation of a 47-item survey that was then disseminated and completed by 55 primary care clinicians. RESULTS: The focus groups identified provider, system, and patient barriers to obesity care. Lack of obesity training during medical school and residency was associated with lower rates of discussing diet and exercise with obese patients (p < 0.05). Clinicians who watched their own diets vigorously were more likely to calculate BMI for obese patients than other clinicians (42% vs. 13%, p < 0.05). Many barriers identified in previous studies (e.g., attitudes toward obese patients, lack of insurance payments for obesity care) were not prevalent barriers in the current study. CONCLUSION: Many VHA clinicians do not routinely provide weight management services for obese patients. The most prevalent barriers to obesity care were poor education during medical school and residency and the lack of information provided by the VHA to both clinicians and patients about available weight management services