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Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is a rare autosomal recessive lysosomal storage disorder caused by mutations in the N-acetylgalactosamine-6-sulfatase (GALNS) gene. We collected, analyzed, and uniformly summarized all published GALNS gene variants, thus updating the previous mutation review (published in 2014). In addition, new variants were communicated by seven reference laboratories in Europe, the Middle East, Latin America, Asia, and the United States. All data were analyzed to determine common alleles, geographic distribution, level of homozygosity, and genotype-phenotype correlation. Moreover, variants were classified according to their pathogenicity as suggested by ACMG. Including those previously published, we assembled 446 unique variants, among which 68 were novel, from 1190 subjects (including newborn screening positive subjects). Variants' distribution was missense (65.0%), followed by nonsense (8.1%), splicing (7.2%), small frameshift deletions(del)/insertions(ins) (7.0%), intronic (4.0%), and large del/ins and complex rearrangements (3.8%). Half (50.4%) of the subjects were homozygous, 37.1% were compound heterozygous, and 10.7% had only one variant detected. The novel variants underwent in silico analysis to evaluate their pathogenicity. All variants were submitted to ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) to make them publicly available. Mutation updates are essential for the correct molecular diagnoses, genetic counseling, prenatal and preimplantation diagnosis, and disease management.

CT scans are an integral component of modern radiotherapy treatments, enabling the accurate localisation of the treatment target and organs-at-risk, and providing the tissue density information required for dose calculations in the treatment planning system. For these reasons, it is important to ensure exposures are optimised to give the required clinical image quality with doses that are as low as reasonably achievable. However, there is little guidance on dose levels in radiotherapy CT imaging either within the UK or internationally. This IPEM topical report presents the results of the first UK wide survey of dose indices in radiotherapy CT planning scans. Patient dose indices were collected for prostate, gynaecological, breast, 3D-lung, 4D-lung, brain and head/neck scans. Median values per scanner and examination type were calculated and national dose reference levels and 'achievable levels' of CT dose index (CTDIvol), dose-length-product (DLP) and scan length are proposed based on the third quartile and median values of these distributions, respectively. A total of 68 radiotherapy CT scanners were included in this audit. The proposed dose reference levels for CTDIvol and DLP are; prostate 16 mGy and 570 mGy.cm, gynaecological 16 mGy and 610 mGy.cm, breast 10 mGy and 390 mGy.cm, 3D-lung 14 mGy and 550 mGy.cm, 4D-lung 63 mGy and 1750 mGy.cm, brain 50 mGy and 1500 mGy.cm and head/neck 49 mGy and 2150 mGy.cm. Significant variations in dose indices were noted, with head/neck and 4D-lung yielding a factor of eighteen difference between the lowest and highest dose scanners. There was also evidence of some clustering in the data by scanner manufacturer, which may be indicative of a lack of local optimisation of individual systems to the clinical task. It is anticipated that providing this data to the UK and wider radiotherapy community will aid the optimisation of treatment planning CT scan protocols.

The energy-loss spectrum associated with scattering of 100 keV H+ ions from Y atoms on Si (111) has been investigated both experimentally and theoretically. Measurements were made from Y overlayers, and from the Si (111) (1X1) two-dimensional silicide phase formed by Y on this surface, in various scattering geometries and with different surface preparations. Theoretical simulations were conducted based on calculations of the energy loss experienced in specific ion trajectories through the surface, using coupled-channel calculations to describe inner-shell ionization and excitation as a function of impact parameter. The experimental results indicate that additional broadening contributions arise from surface inhomogeneity and roughness, but for near-normal incident and outgoing trajectories the theory and experiment agree quite well. The calculations show that, even for the ideal two-dimensional silicide phase in which the Y atoms lie just below the surface, significant energy loss arises from interaction of the ions with surrounding Si atoms, leading to a complete loss of intensity at zero energy loss.