Sibling screening in suspected abusive head trauma : a proposed guideline

Abusive head trauma (AHT) is the leading cause of death from child abuse in children younger than 5 years. It is well documented that the infant contacts of children presenting with suspected AHT are at an increased risk of abuse when compared to the general infant population. Despite this association, a paucity of literature stratifies this risk and translates it to the clinic such that this high-risk group is stringently screened for abusive injuries. In this light, the authors propose a standardised screening method for all contact children of the index case and call for further consensus on the subject

The non-invasive biopsy: will urinary proteomics make the renal tissue biopsy redundant?

Proteomics is a rapidly advancing technique which gives a functional insight into gene expression in living organisms. Urine is an ideal medium for study as it is readily available, easily obtained and less complex than other bodily fluids. Considerable progress has been made over the last 5 years in the study of urinary proteomics as a diagnostic tool for renal disease. The advantages of this technique over the traditional renal biopsy include accessibility, safety, the possibility of serial sampling, and the potential for non-invasive prognostic and diagnostic monitoring of disease and an individual’s response to treatment. Urinary proteomics is now moving from a discovery phase in small studies to a validation phase in much larger numbers of patients with renal disease. Whilst there are still some limitations in methodology, which are assessed in this review, the possibility of urinary proteomics replacing the invasive tissue biopsy for diagnosis of renal disease is becoming increasingly realistic

Terrestrial modification of the Ivuna meteorite and a reassessment of the chemical composition of the CI type specimen

The rare CI carbonaceous chondrites are the most aqueously altered and chemically primitive meteorites but due to their porous nature and high abundance of volatile elements are susceptible to terrestrial weathering. The Ivuna meteorite, type specimen for the CI chondrites, is the largest twentieth-century CI fall and probably the CI chondrite least affected by terrestrial alteration that is available for study. The main mass of Ivuna (BM2008 M1) has been stored in a nitrogen atmosphere at least since its arrival at the Natural History Museum (NHM), London, in 2008 (70 years after its fall) and could be considered the most pristine CI chondrite stone. We report the mineralogy, petrography and bulk elemental composition of BM2008 M1 and a second Ivuna stone (BM1996 M4) stored in air within wooden cabinets. We find that both Ivuna stones are breccias consisting of multiple rounded, phyllosilicate-rich clasts that formed through aqueous alteration followed by impact processing. A polished thin section of BM2008 M1 analysed immediately after preparation was found to contain sulphate-bearing veins that formed when primary sulphides reacted with oxygen and atmospheric water. A section of BM1996 M4 lacked veins but had sulphate grains on the surface that formed in ≤6 years, ∼3 times faster than previous reports for CI chondrite sections. Differences in the extent of terrestrial alteration recorded by BM2008 M1 and BM1996 M4 probably reflect variations in the post-recovery curation history of the stones prior to entering the NHM collection, and indicate that where possible pristine samples of hydrated carbonaceous should be kept out of the terrestrial environment in a stable atmosphere to avoid modification. The bulk elemental composition of the two Ivuna stones show some variability due to their heterogeneous nature but in general are similar to previous analyses of CI chondrites. We combine our elemental abundances with literature values to calculate a new average composition for the Ivuna meteorite, which we find is in good agreement with existing compilations of element compositions in the CI chondrites and the most recent solar photospheric abundances

Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

Heavy element production in a compact object merger observed by JWST

The mergers of binary compact objects such as neutron stars and black holes are of central interest to several areas of astrophysics, including as the progenitors of gamma-ray bursts (GRBs)1, sources of high-frequency gravitational waves (GW)2 and likely production sites for heavy element nucleosynthesis via rapid neutron capture (the r-process)3. Here we present observations of the exceptionally bright gamma-ray burst GRB 230307A. We show that GRB 230307A belongs to the class of long-duration gamma-ray bursts associated with compact object mergers4–6, and contains a kilonova similar to AT2017gfo, associated with the gravitational-wave merger GW1708177–12. We obtained James Webb Space Telescope mid-infrared (mid-IR) imaging and spectroscopy 29 and 61 days after the burst. The spectroscopy shows an emission line at 2.15 microns which we interpret as tellurium (atomic mass A=130), and a very red source, emitting most of its light in the mid-IR due to the production of lanthanides. These observations demonstrate that nucleosynthesis in GRBs can create r-process elements across a broad atomic mass range and play a central role in heavy element nucleosynthesis across the Universe

Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features

The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom’s 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity. We demonstrate the relationship of these features with clinical outcome and show that integration of 186 distinct recurrent genomic alterations defines five genomic subgroups that associate with response to therapy, refining conventional outcome prediction. While requiring independent validation, our findings highlight the potential of whole-genome sequencing to inform future risk stratification in chronic lymphocytic leukemia

Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference

The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique\u2014Subtype and Stage Inference (SuStaIn)\u2014able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer\u2019s disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 7 10 124 ) or temporal stage (p = 3.96 7 10 125 ). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine