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Trials in children with chronic kidney disease do not consistently report outcomes that are critically important to patients and caregivers. This can diminish the relevance and reliability of evidence for decision making, limiting the implementation of results into practice and policy. As part of the Standardized Outcomes in Nephrology—Children and Adolescents (SONG-Kids) initiative, we convened 2 consensus workshops in San Diego, California (7 patients, 24 caregivers, 43 health professionals) and Melbourne, Australia (7 patients, 23 caregivers, 49 health professionals). This report summarizes the discussions on the identification and implementation of the SONG-Kids core outcomes set. Four themes were identified; survival and life participation are common high priority goals, capturing the whole child and family, ensuring broad relevance across the patient journey, and requiring feasible and valid measures. Stakeholders supported the inclusion of mortality, infection, life participation, and kidney function as the core outcomes domains for children with chronic kidney disease.

Understanding the mechanisms leading to new traits or additional features in organisms is a fundamental goal of evolutionary biology. We show that HOXDB regulatory changes have been used repeatedly in different fish genera to alter the length and number of the prominent dorsal spines used to classify stickleback species. In Gasterosteus aculeatus (typically ‘three-spine sticklebacks’), a variant HOXDB allele is genetically linked to shortening an existing spine and adding an additional spine. In Apeltes quadracus (typically ‘four-spine sticklebacks’), a variant HOXDB allele is associated with lengthening a spine and adding an additional spine in natural populations. The variant alleles alter the same non-coding enhancer region in the HOXDB locus but do so by diverse mechanisms, including single-nucleotide polymorphisms, deletions and transposable element insertions. The independent regulatory changes are linked to anterior expansion or contraction of HOXDB expression. We propose that associated changes in spine lengths and numbers are partial identity transformations in a repeating skeletal series that forms major defensive structures in fish. Our findings support the long-standing hypothesis that natural Hox gene variation underlies key patterning changes in wild populations and illustrate how different mutational mechanisms affecting the same region may produce opposite gene expression changes with similar phenotypic outcomes.

This is a protocol for a Cochrane Review (prognosis). The objectives are as follows: To (a) identify the gut microbial biomarkers in patients with CKD, on dialysis, and with kidney transplants; (b) determine whether these biomarkers are associated independently with adverse patient‐relevant outcomes leading to progression of CKD stages 1 to 5; and (c) explore sources of heterogeneity. INVESTIGATION OF SOURCES OF HETEROGENEITY BETWEEN STUDIES: We will explore potential sources of heterogeneity that may impact outcomes such as differences in study participation; stage of CKD (KDIGO 2013; Appendix 1); study design (cohort, case series, case study), timing of outcome measurements; units and instruments of outcome measurements; and length of follow‐up.

SummaryUnderstanding the genetic mechanisms leading to new traits is a fundamental goal of evolutionary biology. We show that HOXDB regulatory changes have been used repeatedly in different stickleback fish species to alter the length and number of bony dorsal spines. In Gasterosteus aculeatus, a variant HOXDB allele is genetically linked to shortening an existing spine and adding a spine. In Apeltes quadracus, a variant allele is associated with lengthening an existing spine and adding a spine. The alleles alter the same conserved non-coding HOXDB enhancer by diverse molecular mechanisms, including SNPs, deletions, and transposable element insertions. The independent cis-acting regulatory changes are linked to anterior expansion or contraction of HOXDB expression. Our findings support the long-standing hypothesis that natural Hox gene variation underlies key morphological patterning changes in wild populations and illustrate how different mutational mechanisms affecting the same region may produce opposite gene expression changes with similar phenotypic outcomes.Abstract Figure

Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes functional elements that descended from previously neutral regions. Here, we demonstrate that the fastest-evolved regions of the human genome, which we term "human ancestor quickly evolved regions" (HAQERs), rapidly diverged in an episodic burst of directional positive selection prior to the human-Neanderthal split, before transitioning to constraint within hominins. HAQERs are enriched for bivalent chromatin states, particularly in gastrointestinal and neurodevelopmental tissues, and genetic variants linked to neurodevelopmental disease. We developed a multiplex, single-cell in vivo enhancer assay to discover that rapid sequence divergence in HAQERs generated hominin-unique enhancers in the developing cerebral cortex. We propose that a lack of pleiotropic constraints and elevated mutation rates poised HAQERs for rapid adaptation and subsequent susceptibility to disease.

To determine the association of socioeconomic disadvantage and parent-rated health in children with chronic kidney disease (CKD). A total of 377 children (aged 6–18 years) with CKD stages I–V (n = 199), on dialysis (n = 43), or with a kidney transplant (n = 135) were recruited from 2012 to 2016 in Australia and New Zealand. Associations of five socioeconomic status (SES) components and the global SES index with parent-rated health of the child were examined using adjusted logistic regression. The median age of participants was 12.6 years (interquartile range (IQR) 8.9–15.5). In the entire cohort, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for poor parent-rated health were 1.85 (1.13–3.03) for lower household income, 1.78 (1.08–2.96) for families that did not own their own home, 2.50 (1.50–4.16) for caregivers who rated their financial status as poor, 0.84 (0.51–1.38) for lower educational attainment, and 1.68 (1.04–2.72) for children whose primary caregivers were unemployed. With reference to the highest global SES index quartile, adjusted ORs for poor parent-rated health in descending order were 1.49 (0.69–3.21), 2.11 (1.06–4.20), and 2.20 (1.09–4.46), respectively. The association between low SES and poor parent-rated health was modified by CKD stage, where lower global SES index was independently associated with poor parent-rated health in children with CKD stages I–V, but not children on dialysis or with kidney transplants (p = 0.04). Low SES is associated with poor parent-rated health in children with CKD stages I–V, but not children on dialysis and with kidney transplants.