Developmental haemostasis is a concept, now universally accepted, introduced by Andrew et al. in the late 1980's. However, coagulation analysers and reagents have changed significantly over the past 15 years. Coagulation testing is known to be sensitive to changes in individual reagents and analysers. We hypothesised that the reference ranges developed by Andrew et al. may not be appropriate for use in a modern coagulation laboratory. Our study was designed to determine whether a current day coagulation testing system (STA Compact analyser and Diagnostica Stago reagent system) was sensitive to age-related changes in coagulation assays. This is the first large scale study since Andrew et al. to determine the age associated numerical changes in coagulation proteins. Our results confirm the concepts of developmental haemostasis elucidated by Andrew et al. However, our results clearly demonstrate that the absolute values of reference ranges for coagulation assays in neonates and children vary with analyser and reagent systems. The results confirm the need for coagulation laboratories to develop age-related reference ranges specific to their own testing systems. Without this, accurate diagnosis and management of neonates and children with suspected bleeding or clotting disorders is not possible. Finally we present age related reference ranges for D-dimers, TFPI, and endogenous thrombin potential, previously not described.

ABSTRACT.Background. There is controversy regarding whether hypersensitivity to food proteins contributes to colic among breastfed infants.Methods. A randomized, controlled trial of a lowallergen maternal diet was conducted among exclusively breastfed infants presenting with colic. In the active arm, mothers excluded cow's milk, eggs, peanuts, tree nuts, wheat, soy, and fish from their diet; mothers in the control group continued to consume these foods. Outcomes were assessed after 7 days, as the change in cry/fuss duration over 48 hours, with validated charts. The primary end point was a reduction in cry/fuss duration of >25% from baseline. Mothers also assessed the responses to diet with categorical and visual analog scales.Results. Of 107 infants, 90 completed the trial (mean age: 5.7 weeks; range: 2.9 -8.6 weeks; 54 male infants). Infants in both groups presented with significant distress (geometric mean: low-allergen group: 690 minutes per 48 hours; control group: 631 minutes per 48 hours). In follow-up assessments on days 8 and 9, there were significantly more responders in the low-allergen group (74% vs 37%), ie, an absolute risk reduction of 37% (95% confidence interval: 18 -56%). Cry/fuss duration per 48 hours was reduced by a substantially greater amount in the low-allergen group; the adjusted geometric mean ratio was 0.79 (95% confidence interval: 0.63-0.97), ie, an average reduction of 21% (95% confidence interval: 3-37%). Mothers' subjective assessments of the responses to diet indicated little difference between the groups.Conclusion. Exclusion of allergenic foods from the maternal diet was associated with a reduction in distressed behavior among breastfed infants with colic presenting in the first 6 weeks of life.

Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles and interactions within tissue neighbourhoods1. Here we applied multiple single-cell and single-nucleus assays (>400,000 nuclei or cells) and spatial imaging technologies to a broad spectrum of healthy reference kidneys (45 donors) and diseased kidneys (48 patients). This has provided a high-resolution cellular atlas of 51 main cell types, which include rare and previously undescribed cell populations. The multi-omic approach provides detailed transcriptomic profiles, regulatory factors and spatial localizations spanning the entire kidney. We also define 28 cellular states across nephron segments and interstitium that were altered in kidney injury, encompassing cycling, adaptive (successful or maladaptive repair), transitioning and degenerative states. Molecular signatures permitted the localization of these states within injury neighbourhoods using spatial transcriptomics, while large-scale 3D imaging analysis (around 1.2 million neighbourhoods) provided corresponding linkages to active immune responses. These analyses defined biological pathways that are relevant to injury time-course and niches, including signatures underlying epithelial repair that predicted maladaptive states associated with a decline in kidney function. This integrated multimodal spatial cell atlas of healthy and diseased human kidneys represents a comprehensive benchmark of cellular states, neighbourhoods, outcome-associated signatures and publicly available interactive visualizations.

<b><i>Introduction:</i></b> Inflammation is important in the pathogenesis of atherosclerosis. Elevated interleukin-6 (IL-6) is associated with cardiovascular events and also predicts mortality in individuals with CKD. Our goal was to determine the association between IL-6, FGF23, and high-sensitivity C-reactive protein (hsCRP) on coronary artery calcification (CAC) progression and mortality in incident dialysis patients without prior coronary events. <b><i>Methods:</i></b> A prospective cohort of incident adult dialysis participants had CAC measured by ECG-triggered multislice CT scans at baseline and at least 12 months later. Lipids, mineral metabolism markers, FGF23, and inflammatory markers, such as IL-6 and hsCRP, were measured at the baseline visit. <b><i>Results:</i></b> Participants in the high IL-6 tertile had the highest baseline CAC score (133.25 [10.35–466.15]) compared to the low (0.25 [0–212.2]) and intermediate (29.55 [0–182.85]) tertiles. Almost half of the participants with high IL-6 (15 of 32 [46.9%]) experienced progression of CAC compared to participants with low (8 of 32 [25%]) and intermediate (9 of 32 [28.1%]) (<i>p</i> = 0.05) IL-6 levels. Each log increase in IL-6 was associated with increase in death (hazard ratio 2.2, 95% CI: 1.2–3.8; <i>p</i> = 0.01). After adjusting for smoking, age, gender, race, diabetes, phosphate, and baseline calcium score, IL-6 (log) was associated with 2.2 times (95% CI: 1.1–4.6; <i>p</i> = 0.03) increase in death. <b><i>Conclusion:</i></b> IL-6 is associated with progression of CAC and mortality in incident dialysis patients.