ObjectiveThe UK national incidence of nutritional rickets is unknown. We aimed to describe the incidence, presentation and clinical management of children under 16 years with nutritional rickets in the UK presenting to secondary care.MethodsProspective data were collected monthly between March 2015 and March 2017 from 3500 consultant paediatricians using British Paediatric Surveillance Unit methodology. Clinicians completed online clinical questionnaires for cases fitting the surveillance case definition.Results125 cases met the case definition, an annual incidence of 0.48 (95% CI 0.37 to 0.62) per 100 000 children under 16 years. 116 children were under 5 years (annual incidence of 1.39 (95% CI 1.05 to 1.81) per 100 000. Boys (70%) were significantly more affected than girls (30%) (OR 2.17, 95% CI 1.25 to 3.78). The majority were of Black (43%) or South Asian (38%) ethnicity. 77.6% of children were not taking vitamin D supplements despite being eligible. Complications included delayed gross motor development (26.4%), fractures (9.6%), hypocalcaemic seizures (8%) and dilated cardiomyopathy (3%). Two children died (1.6%). In eight cases, rickets was confirmed radiologically and biochemically [raised serum alkaline phosphatase (ALP) and parathyroid hormone (PTH) levels ] but were excluded from the incidence analysis for not meeting the case definition of 25-hydroxyvitamin D of <25 nmol/L.ConclusionThe incidence of nutritional rickets in the UK is lower than expected. Serious complications and unexpected deaths, particularly in Black and South Asian children under 5 years, occurred. Both vitamin D deficiency and dietary calcium deficiency are role players in pathogenesis. Uptake of vitamin D supplementation remains low.

Objective: To assess iodine status and goitre prevalence in a sample of schoolchildren in Melbourne. Design: Cross‐sectional study of urinary iodine excretion and presence of goitre in a sample of schoolchildren from Years 5–12 attending two urban schools. Participants: 607 children aged 11–18 years consented to thyroid gland palpation and 577 provided a urine sample on the day of examination in August 2001. Outcome measure: Iodine status of the study population, based on median urinary iodine values categorised as normal (≥ 100 μg/L), mild (50–99 μg/L) or moderate–severe (< 50 μg/L), and classified according to sex, school year and presence of goitre. Results: 76% (439/577) of students had abnormal urinary iodine values, with 27% (156/577) having values consistent with moderate–severe deficiency. The median urinary iodine excretion for the total group was 70μg/L, with values for school years 5–12 ranging from 62 μg/L (Year 12) to 76 μg/L (Year 9). The median urinary iodine value in girls was lower than that in boys (64μg/L v 82 μg/L), and girls had significantly lower urinary iodine values overall (P < 0.002). There was no association between goitre grade and moderate–severe (< 50 μg/L; P = 0.39) or mild (50–99 μg/L; P = 0.07) urinary iodine deficiency. Conclusions: We found mild iodine deficiency in a cohort of schoolchildren in Melbourne. Our results support other data showing mild iodine deficiency in Sydney and Tasmania and the argument for a national study of iodine nutrition.

Base-modification can occur throughout a transfer RNA molecule; however, elaboration is particularly prevalent at position 34 of the anticodon loop (the wobble position), where it functions to influence protein translation. Previously, we demonstrated that the queuosine modification at position 34 can be substituted with an artificial analogue via the queuine tRNA ribosyltransferase enzyme to induce disease recovery in an animal model of multiple sclerosis. Here, we demonstrate that the human enzyme can recognize a very broad range of artificial 7-deazaguanine derivatives for transfer RNA incorporation. By contrast, the enzyme displays strict specificity for transfer RNA species decoding the dual synonymous NAU/C codons, determined using a novel enzyme-RNA capture-release method. Our data highlight the broad scope and therapeutic potential of exploiting the queuosine incorporation pathway to intentionally engineer chemical diversity into the transfer RNA anticodon.

37Despite food choices being one of the most important factors influencing health, efforts to 38 identify individual food groups and dietary patterns that cause disease have been 39 challenging, with traditional nutritional epidemiological approaches plagued by biases and 40 confounding. After identifying 302 (289 novel) individual genetic determinants of dietary 41 intake in 445,779 individuals in the UK Biobank study, we develop a statistical genetics 42 framework that enables us, for the first time, to directly assess the impact of food choices 43 on health outcomes. We show that the biases which affect observational studies extend 44 also to GWAS, genetic correlations and causal inference through genetics, which can be 45 corrected by applying our methods. Finally, by applying Mendelian Randomization 46 approaches to the corrected results we identify some of the first robust causal associations 47 between eating patterns and risks of cancer, heart disease and obesity, distinguishing 48 between the effects of specific foods or dietary patterns. 49 50 Recently, causal inference has been improved by a large number of studies which use Mendelian 61 Randomization (MR) to assess the causal relationship between one or more exposures and 62 outcomes. In MR, genetic variants are used as instrumental variables to measure the "life-long 63 exposure" to a risk factor 5 . This technique has proven to be extremely powerful, not influenced by 64 represents the unadjusted GWAS associations while the lower panel represents the association with food choices, after 87 adjustment for mediating traits, such as health status. 88 89 90 91 92 Replication for 23 of the 29 traits was sought in two additional UK based cohorts (EPIC-Norfolk 15 93 and Fenland 16 ) totalling up to 32,779 subjects. Despite relatively limited power, we could nominally 94 replicate 104/325 associations at p<0.05 (one-sided test) (32%; p=9.47x10 -54 ). The direction of 95 effect was consistent with that for discovery in 268 of the 325 associations (82%; p=7.82x10 -35 , 96 Binomial test; see Table S5). After prioritization of the genes in each locus (see Methods for details 97 and Supp. Table S4 for the prioritized genes), we noticed that for many genes associated with 98 BMI, the BMI-raising allele was associated with lower reported consumption of energy-dense foods 99 such as meat or fat and with higher consumption of lower-calorie foods. Although the exact 100 mechanism of action of many of these genes is unknown, in the case of MC4R in mice loss-of-101 function K314X mutants show an increase in weight, higher intake of calories and higher 102 preference for a high fat diet 17 , while we observe a lower intake of fat and higher intake of fresh 103 fruit. We thus wondered if this could be due to the effect of higher BMI on food choices instead of 104 the reverse and if this effect might also occur for a broader range of health-related traits. 105 106 Detecting the effects of potential confounders on food frequency data 107To test this hypothesis, we first se...