Skewed X-inactivation is common in the general female population

X-inactivation is a well-established dosage compensation mechanism ensuring that X-chromosomal genes are expressed at comparable levels in males and females. Skewed X-inactivation is often explained by negative selection of one of the alleles. We demonstrate that imbalanced expression of the paternal and maternal X-chromosomes is common in the general population and that the random nature of the X-inactivation mechanism can be sufficient to explain the imbalance. To this end, we analyzed blood-derived RNA and whole-genome sequencing data from 79 female children and their parents from the Genome of the Netherlands project. We calculated the median ratio of the paternal over total counts at all X-chromosomal heterozygous single-nucleotide variants with coverage ≥10. We identified two individuals where the same X-chromosome was inactivated in all cells. Imbalanced expression of the two X-chromosomes (ratios ≤0.35 or ≥0.65) was observed in nearly 50% of the population. The empirically observed skewing is explained by a theoretical model where X-inactivation takes place in an embryonic stage in which eight cells give rise to the hematopoietic compartment. Genes escaping X-inactivation are expressed from both alleles and therefore demonstrate less skewing than inactivated genes. Using this characteristic, we identified three novel escapee genes (SSR4, REPS2, and SEPT6), but did not find support for many previously reported escapee genes in blood. Our collective data suggest that skewed X-inactivation is common in the general population. This may contribute to manifestation of symptoms in carriers of recessive X-linked disorders. We recommend that X-inactivation results should not be used lightly in the interpretation of X-linked variants

Promoting professional behaviour in undergraduate medical, dental and veterinary curricula in the Netherlands: Evaluation of a joint effort

Background: From 2002 onwards, a nationwide working group of representatives from all medical (8), dental (3) and veterinary medicine (1) schools collaborated in order to develop and implement recommendations for teaching and assessing professional behaviour. Aim: The aim of this article is to describe the outcomes of this process, including hurdles encountered and challenges to be met. Method: By a qualitative survey, information was requested on teaching professional behaviour, assessment, instruments used, consequences of unprofessional behaviour and faculty training. Results: All schools have adopted at least parts of the 2002 recommendations. Differences exist mainly in the organisational structure of teaching and assessment as well as in the assessment instruments used. In all schools a longitudinal assessment of professional behaviour was accomplished. Conclusion: All schools involved have made progress since 2002 with regard to teaching and assessment of professional behaviour, resulting in a shift from an instrumental to a cultural change for some schools. A stimulating factor was society's call to focus on patient safety and therefore on assessment of unprofessional behaviour. Hurdles yet to be taken are the involvement of students in the assessment process, teacher confidence in personal assessment capacities, remediation programmes and logistic and administrative support

Perception of social media behaviour among medical students, residents and medical specialists

Introduction Behaviour is visible in real-life events, but also on social media. While some national medical organizations have published social media guidelines, the number of studies on professional social media use in medical education is limited. This study aims to explore social media use among medical students, residents and medical specialists. Methods An anonymous, online survey was sent to 3844 medical students at two Dutch medical schools, 828 residents and 426 medical specialists. Quantitative, descriptive data analysis regarding demographic data, yes/no questions and Likert scale questions were performed using SPSS. Qualitative data analysis was performed iteratively, independently by two researchers applying the principles of constant comparison, open and axial coding until consensus was reached. Results Overall response rate was 24.8%. Facebook was most popular among medical students and residents; LinkedIn was most popular among medical specialists. Personal pictures and/or information about themselves on social media that were perceived as unprofessional were reported by 31.3% of students, 19.7% of residents and 4.1% of medical specialists. Information and pictures related to alcohol abuse, partying, clinical work or of a sexually suggestive character were considered inappropriate. Addressing colleagues about their unprofessional posts was perceived to be mainly dependent on the nature and hierarchy of the interprofessional relation. Discussion There is a widespread perception that the presence of unprofessional information on social media among the participants and their colleagues is a common occurrence. Medical educators should create awareness of the risks of unprofessional (online) behaviour among healthcare professionals, as well as the necessity and ways of addressing colleagues in case of such lapses

Maternal trauma but not perinatal depression predicts infant-parent attachment

Understanding if maternal depression is a predictor of infant-parent attachment classification is important to furthering knowledge about the early pathways and predictors of socio-emotional development. Yet few studies that have utilised the Strange Situation Procedure, the gold standard for measurement of infant-parent attachment, have examined antenatal depression as a predictor of attachment, and none has also included a measure of maternal trauma. This study uses data on 224 women recruited in early pregnancy and followed up until 12 months postpartum. Maternal depression was measured in pregnancy using the Structured Clinical Interview for the DSM and repeat Edinburgh Postnatal Depression Scale as well as Stressful Life Events scale across pregnancy and postpartum including items on domestic violence. A past history of trauma was measured using the Childhood Trauma Questionnaire. Attachment was measured using the Strange Situation Procedure (SSP) at 12 months postpartum. We found that maternal depression was not associated with insecure or disorganized attachment. However, a maternal history of childhood trauma and current domestic violence both predicted insecure-avoidant attachment at 12 months, whereas increased number of stressful life events prior to conception and in pregnancy was associated with insecure-resistant attachment. Neither trauma, past or current, nor depression predicted disorganized attachment. In the first study to have included measures of antenatal depression, maternal childhood trauma, and current stressful events as predictors of infant attachment measured using the SSP, we found maternal experiences of past and current trauma but not depression were significant predictors of infant-parent attachment security