Genome wide association studies for carcass traits measured by video image analysis in crossbred lambs

This is the first UK genome wide association study investigating potential links between Video Image Analysis (VIA) carcass traits and molecular polymorphisms in crossbred sheep. Phenotypic and genotypic data were collected from two crossbred lamb populations: Texel x Scotch Mule (TxSM, n = 2330) and Texel x Lleyn (TxL, n = 3816). Traits measured included live weights at birth, eight weeks and weaning (∼15 weeks). VIA-predicted traits included total weights and weights of fat, muscle and bone in the whole carcass and primal (hind leg, saddle, shoulder) regions. Within-breed heritabilities estimated for the VIA traits ranged from 0.01 to 0.70, indicating potential for inclusion of some traits in breeding programmes. The two crossbred populations differed in SNPs associated with different traits. Two SNPs on chromosomes two (s74618.1) and eight (s68536.1), respectively, reached genome-wise significance for TxSM, explaining &lt;1% of trait variance, for whole carcass fat and muscle weights, hind leg and saddle fat weights and shoulder bone weights. For TxL, four SNPs reached genome-wise significance, on chromosome two for hind leg muscle weight (OAR2_117,959,202 and OAR2_11804335), on chromosome 10 for whole carcass bone weight (OAR19_8,995,957.1), and on chromosome 19 for weaning weight (s40847.1), each explaining &lt;1% of trait genetic variation. Differences in apparent genetic control of carcass traits may be influenced by the lambs' cross-breed, but also by management decisions affecting environmental variance and trait definitions, which should be understood in order to define protocols for incorporation of carcass traits into (cross)breeding programmes. Implications: Combining VIA-measured carcass traits with conventional production traits in a breeding programme could potentially improve the production and product quality of meat sheep. Phenotypes for VIA traits could be collected relatively easily if VIA machines were present at all abattoir sites. The current study and future Genome Wide Association Studies may help to identify potentially informative molecular markers, that explain large proportions of the genetic variance observed in VIA-measured carcass traits. Including this information in the estimation of breeding values could increase the accuracy of prediction, increasing the potential rate of genetic improvement for product quality. This study confirms the polygenic architecture of the investigated carcass traits, with a small number of molecular markers that each explain a small amount of genetic variation. Further studies across breed types are recommended to further test and validate molecular markers for traits related to lamb carcass quality, as measured by video image analysis.</p

Heparan sulfate phage display antibodies recognise epitopes defined by a combination of sugar sequence and cation binding.

Phage display antibodies are widely used to follow heparan sulfate (HS) expression in tissues and cells. We demonstrate by ELISA, that cations alter phage display antibody binding profiles to HS and this is mediated by changes in polysaccharide conformation, demonstrated by circular dichroism spectroscopy. Native HS structures, expressed on the cell surfaces of neuroblastoma and fibroblast cells, also exhibited altered antibody binding profiles following exposure to low mM concentrations of these cations. Phage display antibodies recognise conformationally-defined HS epitopes, rather than sequence alone, as has been assumed, and resemble proteins in being sensitive to changes in both charge distribution and conformation following binding of cations to HS polysaccharides

The ‘Dark Side’ and ‘Bright Side’ of Personality: When Too Much Conscientiousness and Too Little Anxiety Are Detrimental with Respect to the Acquisition of Medical Knowledge and Skill

Theory suggests that personality traits evolved to have costs and benefits, with the effectiveness of a trait dependent on how these costs and benefits relate to the present circumstances. This suggests that traits that are generally viewed as positive can have a ‘dark side’ and those generally viewed as negative can have a ‘bright side’ depending on changes in context. We test this in a sample of 220 UK medical students with respect to associations between the Big 5 personality traits and learning outcomes across the 5 years of a medical degree. The medical degree offers a changing learning context from pre-clinical years (where a more methodical approach to learning is needed) to the clinical years (where more flexible learning is needed, in a more stressful context). We argue that while trait conscientiousness should enhance pre-clinical learning, it has a ‘dark side’ reducing the acquisition of knowledge in the clinical years. We also suggest that anxiety has a ‘bright side’ enhancing the acquisition of skills in the clinical years. We also explore if intelligence enhances learning across the medical degree. Using confirmatory factor analysis and structural equation modelling we show that medical skills and knowledge assessed in the pre-clinical and clinical years are psychometrically distinguishable, forming a learning ‘backbone’, whereby subsequent learning outcomes are predicted by previous ones. Consistent with our predictions conscientiousness enhanced preclinical knowledge acquisition but reduced the acquisition of clinical knowledge and anxiety enhanced the acquisition of clinical skills. We also identified a curvilinear U shaped association between Surgency (extraversion) and pre-clinical knowledge acquisition. Intelligence predicted initial clinical knowledge, and had a positive total indirect effect on clinical knowledge and clinical skill acquisition. For medical selection, this suggests that selecting students high on conscientiousness may be problematic, as it may be excluding those with some degree of moderate anxiety

Profiling strugglers in a graduate-entry medicine course at Nottingham: a retrospective case study

Background 10-15% of students struggle at some point in their medicine course. Risk factors include weaker academic qualifications, male gender, mental illness, UK ethnic minority status, and poor study skills. Recent research on an undergraduate medicine course provided a toolkit to aid early identification of students likely to struggle, who can be targeted by established support and study interventions. The present study sought to extend this work by investigating the number and characteristics of strugglers on a graduate-entry medicine (GEM) programme. Methods A retrospective study of four GEM entry cohorts (2003–6) was carried out. All students who had demonstrated unsatisfactory progress or left prematurely were included. Any information about academic, administrative, personal, or social difficulties, were extracted from their course progress files into a customised database and examined. Results 362 students were admitted to the course, and 53 (14.6%) were identified for the study, of whom 15 (4.1%) did not complete the course. Students in the study group differed from the others in having a higher proportion of 2ii first degrees, and scoring less well on GAMSAT, an aptitude test used for admission. Within the study group, it proved possible to categorise students into the same groups previously reported (struggler throughout, pre-clinical struggler, clinical struggler, health-related struggler, borderline struggler) and to identify the majority using a number of flags for early difficulties. These flags included: missed attendance, unsatisfactory attitude or behaviour, health problems, social/family problems, failure to complete immunity status checks, and attendance at academic progress committee. Conclusions Problems encountered in a graduate-entry medicine course were comparable to those reported in a corresponding undergraduate programme. A toolkit of academic and non-academic flags of difficulty can be used for early identification of many who will struggle, and could be used to target appropriate support and interventions

Construct-level predictive validity of educational attainment and intellectual aptitude tests in medical student selection: meta-regression of six UK longitudinal studies

Background: Measures used for medical student selection should predict future performance during training. A problem for any selection study is that predictor-outcome correlations are known only in those who have been selected, whereas selectors need to know how measures would predict in the entire pool of applicants. That problem of interpretation can be solved by calculating construct-level predictive validity, an estimate of true predictor-outcome correlation across the range of applicant abilities. Methods: Construct-level predictive validities were calculated in six cohort studies of medical student selection and training (student entry, 1972 to 2009) for a range of predictors, including A-levels, General Certificates of Secondary Education (GCSEs)/O-levels, and aptitude tests (AH5 and UK Clinical Aptitude Test (UKCAT)). Outcomes included undergraduate basic medical science and finals assessments, as well as postgraduate measures of Membership of the Royal Colleges of Physicians of the United Kingdom (MRCP(UK)) performance and entry in the Specialist Register. Construct-level predictive validity was calculated with the method of Hunter, Schmidt and Le (2006), adapted to correct for right-censorship of examination results due to grade inflation. Results: Meta-regression analyzed 57 separate predictor-outcome correlations (POCs) and construct-level predictive validities (CLPVs). Mean CLPVs are substantially higher (.450) than mean POCs (.171). Mean CLPVs for first-year examinations, were high for A-levels (.809; CI: .501 to .935), and lower for GCSEs/O-levels (.332; CI: .024 to .583) and UKCAT (mean = .245; CI: .207 to .276). A-levels had higher CLPVs for all undergraduate and postgraduate assessments than did GCSEs/O-levels and intellectual aptitude tests. CLPVs of educational attainment measures decline somewhat during training, but continue to predict postgraduate performance. Intellectual aptitude tests have lower CLPVs than A-levels or GCSEs/O-levels. Conclusions: Educational attainment has strong CLPVs for undergraduate and postgraduate performance, accounting for perhaps 65% of true variance in first year performance. Such CLPVs justify the use of educational attainment measure in selection, but also raise a key theoretical question concerning the remaining 35% of variance (and measurement error, range restriction and right-censorship have been taken into account). Just as in astrophysics, ‘dark matter’ and ‘dark energy’ are posited to balance various theoretical equations, so medical student selection must also have its ‘dark variance’, whose nature is not yet properly characterized, but explains a third of the variation in performance during training. Some variance probably relates to factors which are unpredictable at selection, such as illness or other life events, but some is probably also associated with factors such as personality, motivation or study skills