The potential distribution of Bacillus anthracis suitability across Uganda using INLA.

To reduce the veterinary, public health, environmental, and economic burden associated with anthrax outbreaks, it is vital to identify the spatial distribution of areas suitable for Bacillus anthracis, the causative agent of the disease. Bayesian approaches have previously been applied to estimate uncertainty around detected areas of B. anthracis suitability. However, conventional simulation-based techniques are often computationally demanding. To solve this computational problem, we use Integrated Nested Laplace Approximation (INLA) which can adjust for spatially structured random effects, to predict the suitability of B. anthracis across Uganda. We apply a Generalized Additive Model (GAM) within the INLA Bayesian framework to quantify the relationships between B. anthracis occurrence and the environment. We consolidate a national database of wildlife, livestock, and human anthrax case records across Uganda built across multiple sectors bridging human and animal partners using a One Health approach. The INLA framework successfully identified known areas of species suitability in Uganda, as well as suggested unknown hotspots across Northern, Eastern, and Central Uganda, which have not been previously identified by other niche models. The major risk factors for B. anthracis suitability were proximity to water bodies (0-0.3 km), increasing soil calcium (between 10 and 25 cmolc/kg), and elevation of 140-190 m. The sensitivity of the final model against the withheld evaluation dataset was 90% (181 out of 202 = 89.6%; rounded up to 90%). The prediction maps generated using this model can guide future anthrax prevention and surveillance plans by the relevant stakeholders in Uganda.

Clinical presentation of 6q24 transient neonatal diabetes mellitus (6q24 TNDM) and genotype-phenotype correlation in an international cohort of patients.

AIMS/HYPOTHESIS: 6q24 transient neonatal diabetes mellitus (TNDM) is a rare form of diabetes presenting in the neonatal period that remits during infancy but, in a proportion of cases, recurs in later life. We aim to describe the clinical presentation of 6q24 TNDM in the largest worldwide cohort of patients with defined molecular aetiology, in particular seeking differences in presentation or clinical history between aetiological groups. METHODS: One-hundred and sixty-three patients with positively diagnosed 6q24 TNDM were ascertained from Europe, the Americas, Asia and Australia. Clinical data from referrals were recorded and stratified by the molecular aetiology of patients. RESULTS: 6q24 TNDM patients presented at a modal age of one day, with growth retardation and hyperglycaemia, irrespective of molecular aetiology. There was a positive correlation between age of presentation and gestational age, and a negative correlation between adjusted birthweight SD and age of remission. Congenital anomalies were significantly more frequent in patients with paternal uniparental disomy of chromosome 6 or hypomethylation of multiple imprinted loci defects than in those with 6q24 duplication or isolated hypomethylation defects. Patients with hypomethylation had an excess representation of assisted conception at 15%. CONCLUSIONS/INTERPRETATION: This, the largest case series of 6q24 TNDM published, refines and extends the clinical phenotype of the disorder and confirms its clinical divergence from other monogenic TNDM in addition to identifying previously unreported clinical differences between 6q24 subgroups.