Fitness Cost Associated With Enhanced EPSPS Gene Copy Number and Glyphosate Resistance in an Amaranthus tuberculatus Population

The evolution of resistance to pesticides in agricultural systems provides an opportunity to study the fitness costs and benefits of novel adaptive traits. Here, we studied a population of Amaranthus tuberculatus (common waterhemp), which has evolved resistance to glyphosate. The growth and fitness of seed families with contrasting levels of glyphosate resistance was assessed in the absence of glyphosate to determine their ability to compete for resources under intra- and interspecific competition. We identified a positive correlation between the level of glyphosate resistance and gene copy number for the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) glyphosate target, thus identifying gene amplification as the mechanism of resistance within the population. Resistant A. tuberculatus plants were found to have a lower competitive response when compared to the susceptible phenotypes with 2.76 glyphosate resistant plants being required to have an equal competitive effect as a single susceptible plant. A growth trade-off was associated with the gene amplification mechanism under intra-phenotypic competition where 20 extra gene copies were associated with a 26.5 % reduction in dry biomass. Interestingly, this growth trade-off was mitigated when assessed under interspecific competition from maize

The RESPITE trial: remifentanil intravenously administered patient-controlled analgesia (PCA) versus pethidine intramuscular injection for pain relief in labour: study protocol for a randomised controlled trial

Background The commonest opioid used for pain relief in labour is pethidine (meperidine); however, its effectiveness has long been challenged and the drug has known side effects including maternal sedation, nausea and potential transfer across the placenta to the foetus. Over a third of women receiving pethidine require an epidural due to inadequate pain relief. Epidural analgesia increases the risk of an instrumental vaginal delivery and its associated effects. Therefore, there is a clear need for a safe, effective, alternative analgesic to pethidine. Evidence suggests that remifentanil patient-controlled analgesia (PCA) reduces epidural conversion rates compared to pethidine; however, no trial has yet investigated this as a primary endpoint. We are, therefore, comparing pethidine intramuscular injection to remifentanil PCA in a randomised controlled trial. Methods/design Women in established labour, requesting systemic opioid pain relief, will be randomised to either intravenously administered remifentanil PCA (intervention) or pethidine intramuscular injection (control) in an unblinded, 1:1 individual randomised trial. Following informed consent, 400 women in established labour, who request systemic opioid pain relief, from NHS Trusts across England will undergo a minimised randomisation by a computer or automated telephone system to either pethidine or remifentanil. In order to balance the groups this minimisation is based on four parameters; parity (nulliparous versus multiparous), maternal age (<20, 20 < 30, 30 < 40, 40+ years), ethnicity (South Asian (Pakistani/Indian/Bangladeshi) versus Other) and induced versus spontaneous labour. The effectiveness of pain relief provided by each technique will be recorded every 30 min after time zero, until epidural placement, delivery or transfer to theatre, quantified by Visual Analogue Scale. Incidence of maternal side effects including sedation, delivery mode, foetal distress requiring delivery, neonatal status at delivery and rate of initiation of breastfeeding within the first hour of birth will also be recorded. Maternal satisfaction with her childbirth experience will be determined by a postpartum questionnaire prior to discharge from the delivery ward. Discussion The RESPITE trial’s primary outcome is the proportion of women who have an epidural placed for pain relief in labour in each arm. Trial Registration Current Controlled Trials registration number: ISRCTN29654603. Registered on 23 July 2013

Evaluating the Benefits of Aphasia Intervention Delivered in Virtual Reality: Results of a Quasi-Randomised Study

Introduction This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks’ intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. Results There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings

'It gives you an understanding you can't get from any book.' The relationship between medical students' and doctors' personal illness experiences and their performance: a qualitative and quantitative study

Background: anecdotes abound about doctors' personal illness experiences and the effect they have on their empathy and care of patients. We formally investigated the relationship between doctors' and medical students' personal illness experiences, their examination results, preparedness for clinical practice, learning and professional attitudes and behaviour towards patients.Methods: newly-qualified UK doctors in 2005 (n = 2062/4784), and two cohorts of students at one London medical school (n = 640/749) participated in the quantitative arm of the study. 37 Consultants, 1 Specialist Registrar, 2 Clinical Skills Tutors and 25 newly-qualified doctors participated in the qualitative arm. Newly-qualified doctors and medical students reported their personal illness experiences in a questionnaire. Doctors' experiences were correlated with self-reported preparedness for their new clinical jobs. Students' experiences were correlated with their examination results, and self-reported anxiety and depression. Interviews with clinical teachers, newly-qualified doctors and senior doctors qualitatively investigated how personal illness experiences affect learning, professional attitudes, and behaviour.Results: 85.5% of newly-qualified doctors and 54.4% of medical students reported personal illness experiences. Newly-qualified doctors who had been ill felt less prepared for starting work (p &lt; 0.001), but those who had only experienced illness in a relative or friend felt more prepared (p = 0.02). Clinical medical students who had been ill were more anxious (p = 0.01) and had lower examination scores (p = 0.006). Doctors felt their personal illness experiences helped them empathise and communicate with patients. Medical students with more life experience were perceived as more mature, empathetic, and better learners; but illness at medical school was recognised to impede learning.Conclusion: the majority of the medical students and newly qualified doctors we studied reported personal illness experiences, and these experiences were associated with lower undergraduate examination results, higher anxiety, and lower preparedness. However reflection on such experiences may have improved professional attitudes such as empathy and compassion for patients. Future research is warranted in this area

Achieving sustainable quality in maternity services – using audit of incontinence and dyspareunia to identify shortfalls in meeting standards

BACKGROUND: Some complications of childbirth (for example, faecal incontinence) are a source of social embarrassment for women, and are often under reported. Therefore, it was felt important to determine levels of complications (against established standards) and to consider obstetric measures aimed at reducing them. METHODS: Clinical information was collected on 1036 primiparous women delivering at North and South Staffordshire Acute and Community Trusts over a 5-month period in 1997. A questionnaire was sent to 970 women which included self-assessment of levels of incontinence and dyspareunia prior to pregnancy, at 6 weeks post delivery and 9 to 14 months post delivery. RESULTS: The response rate was 48%(470/970). Relatively high levels of obstetric interventions were found. In addition, the rates of instrumental deliveries differed between the two hospitals. The highest rates of postnatal symptoms had occurred at 6 weeks, but for many women problems were still present at the time of the survey. At 9–14 months high rates of dyspareunia (29%(102/347)) and urinary incontinence (35%(133/382)) were reported. Seventeen women (4%) complained of faecal incontinence at this time. Similar rates of urinary incontinence and dyspareunia were seen regardless of mode of delivery. CONCLUSION: Further work should be undertaken to reduce the obstetric interventions, especially instrumental deliveries. Improvements in a number of areas of care should be undertaken, including improved patient information, improved professional communication and improved professional recognition and management of third degree tears. It is likely that these measures would lead to a reduction in incontinence and dyspareunia after childbirth

A comparison of five methods of measuring mammographic density: a case-control study.

BACKGROUND: High mammographic density is associated with both risk of cancers being missed at mammography, and increased risk of developing breast cancer. Stratification of breast cancer prevention and screening requires mammographic density measures predictive of cancer. This study compares five mammographic density measures to determine the association with subsequent diagnosis of breast cancer and the presence of breast cancer at screening. METHODS: Women participating in the "Predicting Risk Of Cancer At Screening" (PROCAS) study, a study of cancer risk, completed questionnaires to provide personal information to enable computation of the Tyrer-Cuzick risk score. Mammographic density was assessed by visual analogue scale (VAS), thresholding (Cumulus) and fully-automated methods (Densitas, Quantra, Volpara) in contralateral breasts of 366 women with unilateral breast cancer (cases) detected at screening on entry to the study (Cumulus 311/366) and in 338 women with cancer detected subsequently. Three controls per case were matched using age, body mass index category, hormone replacement therapy use and menopausal status. Odds ratios (OR) between the highest and lowest quintile, based on the density distribution in controls, for each density measure were estimated by conditional logistic regression, adjusting for classic risk factors. RESULTS: The strongest predictor of screen-detected cancer at study entry was VAS, OR 4.37 (95% CI 2.72-7.03) in the highest vs lowest quintile of percent density after adjustment for classical risk factors. Volpara, Densitas and Cumulus gave ORs for the highest vs lowest quintile of 2.42 (95% CI 1.56-3.78), 2.17 (95% CI 1.41-3.33) and 2.12 (95% CI 1.30-3.45), respectively. Quantra was not significantly associated with breast cancer (OR 1.02, 95% CI 0.67-1.54). Similar results were found for subsequent cancers, with ORs of 4.48 (95% CI 2.79-7.18), 2.87 (95% CI 1.77-4.64) and 2.34 (95% CI 1.50-3.68) in highest vs lowest quintiles of VAS, Volpara and Densitas, respectively. Quantra gave an OR in the highest vs lowest quintile of 1.32 (95% CI 0.85-2.05). CONCLUSIONS: Visual density assessment demonstrated a strong relationship with cancer, despite known inter-observer variability; however, it is impractical for population-based screening. Percentage density measured by Volpara and Densitas also had a strong association with breast cancer risk, amongst the automated measures evaluated, providing practical automated methods for risk stratification

The effect of a brief social intervention on the examination results of UK medical students: a cluster randomised controlled trial

Background: Ethnic minority (EM) medical students and doctors underperform academically, but little evidence exists on how to ameliorate the problem. Psychologists Cohen et al. recently demonstrated that a written self-affirmation intervention substantially improved EM adolescents' school grades several months later. Cohen et al.'s methods were replicated in the different setting of UK undergraduate medical education.Methods: All 348 Year 3 white (W) and EM students at one UK medical school were randomly allocated to an intervention condition (writing about one's own values) or a control condition (writing about another's values), via their tutor group. Students and assessors were blind to the existence of the study. Group comparisons on post-intervention written and OSCE (clinical) assessment scores adjusted for baseline written assessment scores were made using two-way analysis of covariance. All assessment scores were transformed to z-scores (mean = 0 standard deviation = 1) for ease of comparison. Comparisons between types of words used in essays were calculated using t-tests. The study was covered by University Ethics Committee guidelines.Results: Groups were statistically identical at baseline on demographic and psychological factors, and analysis was by intention to treat [intervention group EM n = 95, W n = 79; control group EM n = 77; W n = 84]. As predicted, there was a significant ethnicity by intervention interaction [F(4,334) = 5.74; p = 0.017] on the written assessment. Unexpectedly, this was due to decreased scores in the W intervention group [mean difference = 0.283; (95% CI = 0.093 to 0.474] not improved EM intervention group scores [mean difference = -0.060 (95% CI = -0.268 to 0.148)]. On the OSCE, both W and EM intervention groups outperformed controls [mean difference = 0.261; (95% CI = -0.047 to -0.476; p = 0.013)]. The intervention group used more optimistic words (p < 0.001) and more "I" and "self" pronouns in their essays (p < 0.001), whereas the control group used more "other" pronouns (p < 0.001) and more negations (p < 0.001).Discussion: Cohen et al.'s finding that a brief self-affirmation task narrowed the ethnic academic achievement gap was replicated on the written assessment but against expectations, this was due to reduced performance in the W group. On the OSCE, the intervention improved performance in both W and EM groups. In the intervention condition, participants tended to write about themselves and used more optimistic words than in the control group, indicating the task was completed as requested. The study shows that minimal interventions can have substantial educational outcomes several months later, which has implications for the multitude of seemingly trivial changes in teaching that are made on an everyday basis, whose consequences are never formally assessed

Incidence and phenotypes of childhood-onset genetic epilepsies:a prospective population-based national cohort

Epilepsy is common in early childhood. In this age group it is associated with high rates of therapy-resistance, and with cognitive, motor, and behavioural comorbidity. A large number of genes, with wide ranging functions, are implicated in its aetiology, especially in those with therapy-resistant seizures. Identifying the more common single-gene epilepsies will aid in targeting resources, the prioritization of diagnostic testing and development of precision therapy. Previous studies of genetic testing in epilepsy have not been prospective and population-based. Therefore, the population-incidence of common genetic epilepsies remains unknown. The objective of this study was to describe the incidence and phenotypic spectrum of the most common single-gene epilepsies in young children, and to calculate what proportion are amenable to precision therapy. This was a prospective national epidemiological cohort study. All children presenting with epilepsy before 36 months of age were eligible. Children presenting with recurrent prolonged (&gt;10 min) febrile seizures; febrile or afebrile status epilepticus (&gt;30 min); or with clusters of two or more febrile or afebrile seizures within a 24-h period were also eligible. Participants were recruited from all 20 regional paediatric departments and four tertiary children’s hospitals in Scotland over a 3-year period. DNA samples were tested on a custom-designed 104-gene epilepsy panel. Detailed clinical information was systematically gathered at initial presentation and during follow-up. Clinical and genetic data were reviewed by a multidisciplinary team of clinicians and genetic scientists. The pathogenic significance of the genetic variants was assessed in accordance with the guidelines of UK Association of Clinical Genetic Science (ACGS). Of the 343 patients who met inclusion criteria, 333 completed genetic testing, and 80/333 (24%) had a diagnostic genetic finding. The overall estimated annual incidence of single-gene epilepsies in this well-defined population was 1 per 2120 live births (47.2/100 000; 95% confidence interval 36.9–57.5). PRRT2 was the most common single-gene epilepsy with an incidence of 1 per 9970 live births (10.0/100 000; 95% confidence interval 5.26–14.8) followed by SCN1A: 1 per 12 200 (8.26/100 000; 95% confidence interval 3.93–12.6); KCNQ2: 1 per 17 000 (5.89/100 000; 95% confidence interval 2.24–9.56) and SLC2A1: 1 per 24 300 (4.13/100 000; 95% confidence interval 1.07–7.19). Presentation before the age of 6 months, and presentation with afebrile focal seizures were significantly associated with genetic diagnosis. Single-gene disorders accounted for a quarter of the seizure disorders in this cohort. Genetic testing is recommended to identify children who may benefit from precision treatment and should be mainstream practice in early childhood onset epilepsy