Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus.

UNC93B1 is a transmembrane domain protein mediating the signaling of endosomal Toll-like receptors (TLRs). We report five families harboring rare missense substitutions (I317M, G325C, L330R, R466S, and R525P) in UNC93B1 causing systemic lupus erythematosus (SLE) or chilblain lupus (CBL) as either autosomal dominant or autosomal recessive traits. As for a D34A mutation causing murine lupus, we recorded a gain of TLR7 and, to a lesser extent, TLR8 activity with the I317M (in vitro) and G325C (in vitro and ex vivo) variants in the context of SLE. Contrastingly, in three families segregating CBL, the L330R, R466S, and R525P variants were isomorphic with respect to TLR7 activity in vitro and, for R525P, ex vivo. Rather, these variants demonstrated a gain of TLR8 activity. We observed enhanced interaction of the G325C, L330R, and R466S variants with TLR8, but not the R525P substitution, indicating different disease mechanisms. Overall, these observations suggest that UNC93B1 mutations cause monogenic SLE or CBL due to differentially enhanced TLR7 and TLR8 signaling.

Predictors of professional behaviour and academic outcomes in a UK medical school: A longitudinal cohort study.

BACKGROUND: Over the past 70 years, there has been a recurring debate in the literature and in the popular press about how best to select medical students. This implies that we are still not getting it right: either some students are unsuited to medicine or the graduating doctors are considered unsatisfactory, or both. AIM: To determine whether particular variables at the point of selection might distinguish those more likely to become satisfactory professional doctors, by following a complete intake cohort of students throughout medical school and analysing all the data used for the students' selection, their performance on a range of other potential selection tests, academic and clinical assessments throughout their studies, and records of professional behaviour covering the entire five years of the course. METHODS: A longitudinal database captured the following anonymised information for every student (n = 146) admitted in 2007 to the Hull York Medical School (HYMS) in the UK: demographic data (age, sex, citizenship); performance in each component of the selection procedure; performance in some other possible selection instruments (cognitive and non-cognitive psychometric tests); professional behaviour in tutorials and in other clinical settings; academic performance, clinical and communication skills at summative assessments throughout; professional behaviour lapses monitored routinely as part of the fitness-to-practise procedures. Correlations were sought between predictor variables and criterion variables chosen to demonstrate the full range of course outcomes from failure to complete the course to graduation with honours, and to reveal clinical and professional strengths and weaknesses. RESULTS: Student demography was found to be an important predictor of outcomes, with females, younger students and British citizens performing better overall. The selection variable "HYMS academic score", based on prior academic performance, was a significant predictor of components of Year 4 written and Year 5 clinical examinations. Some cognitive subtest scores from the UK Clinical Aptitude Test (UKCAT) and the UKCAT total score were also significant predictors of the same components, and a unique predictor of the Year 5 written examination. A number of the non-cognitive tests were significant independent predictors of Years 4 and 5 clinical performance, and of lapses in professional behaviour. First- and second-year tutor ratings were significant predictors of all outcomes, both desirable and undesirable. Performance in Years 1 and 2 written exams did not predict performance in Year 4 but did generally predict Year 5 written and clinical performance. CONCLUSIONS: Measures of a range of relevant selection attributes and personal qualities can predict intermediate and end of course achievements in academic, clinical and professional behaviour domains. In this study HYMS academic score, some UKCAT subtest scores and the total UKCAT score, and some non-cognitive tests completed at the outset of studies, together predicted outcomes most comprehensively. Tutor evaluation of students early in the course also identified the more and less successful students in the three domains of academic, clinical and professional performance. These results may be helpful in informing the future development of selection tools.

Can personal qualities of medical students predict in-course examination success and professional behaviour? An exploratory prospective cohort study.

BACKGROUND: Over two-thirds of UK medical schools are augmenting their selection procedures for medical students by using the United Kingdom Clinical Aptitude Test (UKCAT), which employs tests of cognitive and non-cognitive personal qualities, but clear evidence of the tests' predictive validity is lacking. This study explores whether academic performance and professional behaviours that are important in a health professional context can be predicted by these measures, when taken before or very early in the medical course. METHODS: This prospective cohort study follows the progress of the entire student cohort who entered Hull York Medical School in September 2007, having taken the UKCAT cognitive tests in 2006 and the non-cognitive tests a year later. This paper reports on the students' first and second academic years of study. The main outcome measures were regular, repeated tutor assessment of individual students' interpersonal skills and professional behaviour, and annual examination performance in the three domains of recall and application of knowledge, evaluation of data, and communication and practical clinical skills. The relationships between non-cognitive test scores, cognitive test scores, tutor assessments and examination results were explored using the Pearson product-moment correlations for each group of data; the data for students obtaining the top and bottom 20% of the summative examination results were compared using Analysis of Variance. RESULTS: Personal qualities measured by non-cognitive tests showed a number of statistically significant relationships with ratings of behaviour made by tutors, with performance in each year's objective structured clinical examinations (OSCEs), and with themed written summative examination marks in each year. Cognitive ability scores were also significantly related to each year's examination results, but seldom to professional behaviours. The top 20% of examination achievers could be differentiated from the bottom 20% on both non-cognitive and cognitive measures. CONCLUSIONS: This study shows numerous significant relationships between both cognitive and non-cognitive test scores, academic examination scores and indicators of professional behaviours in medical students. This suggests that measurement of non-cognitive personal qualities in applicants to medical school could make a useful contribution to selection and admission decisions. Further research is required in larger representative groups, and with more refined predictor measures and behavioural assessment methods, to establish beyond doubt the incremental validity of such measures over conventional cognitive assessments.

Use of UKCAT scores in student selection by U.K. medical schools, 2006-2010.

BACKGROUND: The United Kingdom Clinical Aptitude Test (UKCAT) is a set of cognitive tests introduced in 2006, taken annually before application to medical school. The UKCAT is a test of aptitude and not acquired knowledge and as such the results give medical schools a standardised and objective tool that all schools could use to assist their decision making in selection, and so provide a fairer means of choosing future medical students.Selection of students for U.K. medical schools is usually in three stages: assessment of academic qualifications, assessment of further qualities from the application form submitted via UCAS (Universities and Colleges Admissions Service) leading to invitation to interview, and then selection for offer of a place. Medical schools were informed of the psychometric qualities of the UKCAT subtests and given some guidance regarding the interpretation of results. Each school then decided how to use the results within its own selection system. METHODS: Annual retrospective key informant telephone interviews were conducted with every UKCAT Consortium medical school, using a pre-circulated structured questionnaire. The key points of the interview were transcribed, 'member checked' and a content analysis was undertaken. RESULTS: Four equally popular ways of using the test results have emerged, described as Borderline, Factor, Threshold and Rescue methods. Many schools use more than one method, at different stages in their selection process. Schools have used the scores in ways that have sought to improve the fairness of selection and support widening participation. Initially great care was taken not to exclude any applicant on the basis of low UKCAT scores alone but it has been used more as confidence has grown. CONCLUSIONS: There is considerable variation in how medical schools use UKCAT, so it is important that they clearly inform applicants how the test will be used so they can make best use of their limited number of applications.

Cervicofacial nontuberculous mycobacterium lymphadenitis in children: is surgery always necessary?

INTRODUCTION: The optimal treatment of cervicofacial nontuberculous mycobacterium lymphadenitis (CFNTB) in children is yet to be established. There is a general consensus that surgical excision results in a definitive resolution of the disease. The main aim of surgery is to remove affected nodes so that they do not discharge through the skin. Recently there are some investigators who are reporting successful antibiotic treatment and advocating medical therapy as the first line treatment. METHODS: 16 children consecutively presenting to otolaryngology in a tertiary referral centre over an 8-year period with CFNTB. Inclusion criteria were chronic cervicofacial lymphadenitis with either: (1) a culture positive for atypical mycobacteria (from either a lymph node or fine needle aspirate (FNA) specimen); or (2) acid-fast bacilli identified (from either a lymph node or FNA specimen); or (3) post excision histological findings consistent with mycobacterial infection (i.e. non-caseating granulomas) in the absence of other clinical features suggestive of other granulomatous conditions. Lesions with superficial skin change were treated preferentially with surgery. Children presenting with lymph nodes contained deep to sternocleidmastoid were assessed with FNA cytological and microbiological analysis and MRI or CT, and treated preferentially with antibiotics or watchful waiting. RESULTS: 4 children (2 culture positive, 2 with acid-fast bacilli on needle aspirate) presented with lymphadenopathy deep to sternocleidmastoid and were managed non-surgically. All 4 resolved without cutaneous involvement. 11 children with a clinical presentation of CFNTB underwent complete excision of all involved nodes for superficial lesions (6 were culture positive, and all had granulomatous histology). None recurred. 1 patient presented late with a mature, discharging parotid sinus, which was managed with watchful waiting as the lesion was clinically close to natural resolution. CONCLUSIONS: Depth at presentation may help decide which patients with CFNTB can be treated non-surgically without cutaneous sequelae. We propose that a watch and wait management is an option for deep nodes.

MRI visualization of the female pelvis in the plane of the tension-free vaginal tape (TVT) procedure.

We evaluated the distances and angles of the major blood vessels from various pelvic structures in the plane of the tension-free vaginal tape (TVT) procedure in 19 pelvic MR imagies. The major blood vessels were the iliofemoral vessels. The mean distance of the left iliofemoral vessels from the midline was 5.7+/-0.4 cm, and 5.7+/-0.3 cm for the right vessels. The mean distance of the left sacral tuberosities from the midline was 5.5+/-0.4 cm, and 5.6+/-0.3 cm for the right vessels. The angle between the midurethra and the left iliofemoral vessels was 50.6+/-4.4 cm, and 49.6+/-4.0 cm for the right. A significant correlation was found between the distance of the right and left iliofemoral vessels from the midline and the distance of right and left sacral tuberosities from the midline ( P<0.01, P<0.007). We suggest that palpation of the sacral tuberosities might indicate the location of the iliofemoral blood vessels.