Assisting the implementation of screening for type 1 diabetes by using artificial intelligence on publicly available data.

The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals. ASSET (AI for Sustainable Prevention of Autoimmunity in the Society; www.asset.healthcare ) is a public/private consortium that was established to contribute to research around screening for type 1 diabetes and particularly to how AI can drive the implementation of a precision medicine approach to disease prevention. ASSET will additionally focus on issues pertaining to operational implementation of screening. The authors of this article, researchers and clinicians active in the field of type 1 diabetes, met in an open forum to independently debate key issues around screening for type 1 diabetes and to advise ASSET. The potential use of AI in the analysis of longitudinal data from observational cohort studies to inform the design of improved, more individualised screening programmes was also discussed. A key issue was whether AI would allow the research community and industry to capitalise on large publicly available data repositories to design screening programmes that allow the early detection of individuals at high risk and enable clinical evaluation of preventive therapies. Overall, AI has the potential to revolutionise type 1 diabetes screening, in particular to help identify individuals who are at increased risk of disease and aid in the design of appropriate follow-up plans. We hope that this initiative will stimulate further research on this very timely topic.

Effects of lambing season on nematode faecal egg output in ewes.

In this study, we assessed the occurrence of a periparturient rise (PPR) in winter and spring lambing ewes in Sweden and where nematode egg excretion patterns were investigated mainly for diagnostic purposes. Gastrointestinal nematodes and Haemonchus contortus presence were monitored in parallel in all animals in each experimental group on four farms in samples that were collected mainly when the animals were stabled. Faecal examinations of the same animals were conducted on four sampling occasions between January and June 2018 Each group consisted of 12 crossbreed ewes of similar genotype. One group's peak lambing was in January or February (early), and the other in March or early May (late). The first (S1) and third samples (S3) were from approximately one to two weeks before parturition in the early (winter lambing) and late (spring lambing) group respectively, whereas the second (S2) and fourth samples (S4) were collected approximately three to five weeks post-parturition in the same groups. During the course of the study, there was a significant rise in faecal egg counts (FEC) in both groups on all farms. On three farms with a substantial amount of Haemonchus, we observed a difference in the egg excretion patterns between the two groups of ewes as revealed by a significant interaction between the sampling point and lambing period. Also, when samples corresponding to each other in relation to the number of weeks that had elapsed post-parturition (three to five weeks post-parturition, S2 for early and S4 for late) were compared, FEC were significantly lower in the early group lambing in winter than the late group lambing in spring. This indicates that besides lambing, the rise in nematode egg count is also influenced by other factors unrelated to the lambing period, such as the increased daylight in spring. Due to study limitations, we cannot provide a more detailed explanation for this, but only state that the rise appeared to be more closely linked to season than physiology as measured by day relative to parturition. Still, our results suggests that when turned out, winter lambing ewes contribute to pasture contamination to a lesser extent than those lambing in spring. These results will be used in stipulating evidence-based advice to farmers in their flock management to reduce use of anthelmintics, and at the same time efficiently produce prime lambs.

Relationship between Ljungan virus antibodies, HLA-DQ8, and insulin autoantibodies in newly diagnosed type 1 diabetes children.

Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n=676) and controls (n=309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75(th) percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4(th) quartile LVAb were found in 25% (170/676) of which 64% were <10 (n=108, p<0.0001), and 27% were<5 (n=45; p<0.0001) years old. The 4(th) quartile LVAb in children <10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p<0.0001). Furthermore, in the group with 4(th) quartile LVAb, 55% were IAA positive (p=0.01) and correlation was found between 4(th) quartile LVAb and IAA in children <10 years of age (p=0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4(th) quartile LVAb correlated with IAA; and 3) there was a correlation between 4(th) quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.