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Background: The outcome of assessments is determined by the standard‐setting method used. Standard setting is the process of deciding what is good enough. A cutoff score of 50% was commonly used in dental schools in Malaysia. This study aims to compare the conventional, norm‐referenced, and modified‐Angoff standard‐setting methods. Methods: The norm‐referenced method of standard setting was applied to the real scores of 40 final‐year dental students on a multiple‐choice question (MCQ), a short answer question (SAQ), and an objective structured clinical examination (OSCE). A panel of 10 judges set the standard using the modified‐Angoff method for the same paper in one sitting. One judge set the passing score of 10 OSCE questions after 2 weeks. A comparison of the grades and pass/fail rates derived from the absolute standard, norm‐referenced, and modified‐Angoff methods was made. The intra‐rater and inter‐rater reliabilities of the modified‐Angoff method were assessed. Results: The passing rate for the absolute standard was 100% (40/40), for the norm‐referenced method it was 62.5% (25/40), and for the modified‐Angoff method it was 80% (32/40). The modified‐Angoff method had good inter‐rater reliability of 0.876 and excellent test–retest reliability of 0.941. Conclusion: There were significant differences in the outcomes of these three standard‐setting methods, as shown by the difference in the proportion of candidates who passed and failed the assessment. The modified‐Angoff method was found to have good reliability for use with a professional qualifying dental examination. [ABSTRACT FROM AUTHOR]

The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles and restores expression of PPT reporters. In zebrafish, knockdown eif5a partly recapitulates the human phenotype that can be rescued with 1 µM spermidine supplementation. In summary, we uncover the role of eIF5A in human development and disease, demonstrate the mechanistic complexity of EIF5A-related disorder and raise possibilities for its treatment. eIF5A is critical for protein synthesis but has not yet been associated with congenital human disease. Here, the authors show that EIF5A variants cause a Mendelian disorder via reduced eIF5A-ribosome interactions and this phenotype is partially corrected by spermidine supplementation in yeast and zebrafish. [ABSTRACT FROM AUTHOR]

ABSTRACT A rare syndromic form of intellectual disability with impaired speech was recently found associated with mutations in CHAMP1 (chromosome alignment-maintaining phosphoprotein 1), the protein product of which is directly involved in microtubule-kinetochore attachment. Through whole-exome sequencing in six unrelated nonconsanguineous families having a sporadic case of intellectual disability, we identified six novel de novo truncating mutations in CHAMP1: c.1880C>G p.(Ser627*), c.1489C>T; p.(Arg497*), c.1876_1877delAG; p.(Ser626Leufs*4), c.1043G>A; p.(Trp348*), c.1002G>A; p.(Trp334*), and c.958_959delCC; p.(Pro320*). Our clinical observations confirm the phenotypic homogeneity of the syndrome, which represents therefore a distinct clinical entity. Besides, our functional studies show that CHAMP1 protein variants are delocalized from chromatin and are unable to bind to two of its direct partners, POGZ and HP1. These data suggest a pathogenic mechanism of the CHAMP1-associated intellectual disability syndrome mediated by direct interacting partners of CHAMP1, several of which are involved in chromo/kinetochore-related disorders. [ABSTRACT FROM AUTHOR]

Since August 2009, the National Health Service of the United Kingdom has faced the challenge of delivering training for junior doctors within a 48-hour working week, as stipulated by the European Working Time Directive and legislated in the UK by the Working Time Regulations 1998. Since that time, widespread concern has been expressed about the impact of restricted duty hours on the quality of postgraduate medical training in the UK, particularly in the "craft" specialties - that is, those disciplines in which trainees develop practical skills that are best learned through direct experience with patients. At the same time, specialist training in the UK has experienced considerable change since 2007 with the introduction of competency-based specialty curricula, workplace-based assessment, and the annual review of competency progression. The challenges presented by the reduction of duty hours include increased pressure on doctors-in-training to provide service during evening and overnight hours, reduced interaction with supervisors, and reduced opportunities for learning. This paper explores these challenges and proposes potential responses with respect to the reorganization of training and service provision. [ABSTRACT FROM AUTHOR]

Heterozygous mutations of the homeobox genes ALX4 and MSX2 cause skull defects termed enlarged parietal foramina (PFM) and cranium bifidum (CB); a single MSX2 mutation has been documented in a unique craniosynostosis (CRS) family. However, the relative mutational contribution of these genes to PFM/CB and CRS is not known and information on genotype–phenotype correlations is incomplete. We analysed ALX4 and MSX2 in 11 new unrelated cases or families with PFM/CB, 181 cases of CRS, and a single family segregating a submicroscopic deletion of 11p11.2, including ALX4. We explored the correlations between skull defect size and age, gene, and mutation type, and reviewed additional phenotypic manifestations. Four PFM cases had mutations in either ALX4 or MSX2; including previous families, we have identified six ALX4 and six MSX2 mutations, accounting for 11/13 familial, but only 1/6 sporadic cases. The deletion family confirms the delineation of a mental retardation locus to within 1.1 Mb region of 11p11.2. Overall, no significant size difference was found between ALX4- and MSX2-related skull defects, but the ALX4 mutation p.R218Q tends to result in persistent CB and is associated with anatomical abnormalities of the posterior fossa. We conclude that PFM caused by mutations in ALX4 and MSX2 have a similar prevalence and are usually clinically indistinguishable. Mutation screening has a high pickup rate in PFM, especially in familial cases, but is not indicated in CRS.European Journal of Human Genetics (2006) 14, 151–158. doi:10.1038/sj.ejhg.5201526; published online 30 November 2005 [ABSTRACT FROM AUTHOR]