Epigenetic and integrative cross-omics analyses of cerebral white matter hyperintensities on MRI.

Cerebral white matter hyperintensities on MRI are markers of cerebral small vessel disease, a major risk factor for dementia and stroke. Despite the successful identification of multiple genetic variants associated with this highly heritable condition, its genetic architecture remains incompletely understood. More specifically, the role of DNA methylation has received little attention. We investigated the association between white matter hyperintensity burden and DNA methylation in blood at ∼450 000 cytosine-phosphate-guanine (CpG) sites in 9732 middle-aged to older adults from 14 community-based studies. Single CpG and region-based association analyses were carried out. Functional annotation and integrative cross-omics analyses were performed to identify novel genes underlying the relationship between DNA methylation and white matter hyperintensities. We identified 12 single CpG and 46 region-based DNA methylation associations with white matter hyperintensity burden. Our top discovery single CpG, cg24202936 (P = 7.6 × 10-8), was associated with F2 expression in blood (P = 6.4 × 10-5) and co-localized with FOLH1 expression in brain (posterior probability = 0.75). Our top differentially methylated regions were in PRMT1 and in CCDC144NL-AS1, which were also represented in single CpG associations (cg17417856 and cg06809326, respectively). Through Mendelian randomization analyses cg06809326 was putatively associated with white matter hyperintensity burden (P = 0.03) and expression of CCDC144NL-AS1 possibly mediated this association. Differentially methylated region analysis, joint epigenetic association analysis and multi-omics co-localization analysis consistently identified a role of DNA methylation near SH3PXD2A, a locus previously identified in genome-wide association studies of white matter hyperintensities. Gene set enrichment analyses revealed functions of the identified DNA methylation loci in the blood-brain barrier and in the immune response. Integrative cross-omics analysis identified 19 key regulatory genes in two networks related to extracellular matrix organization, and lipid and lipoprotein metabolism. A drug-repositioning analysis indicated antihyperlipidaemic agents, more specifically peroxisome proliferator-activated receptor-alpha, as possible target drugs for white matter hyperintensities. Our epigenome-wide association study and integrative cross-omics analyses implicate novel genes influencing white matter hyperintensity burden, which converged on pathways related to the immune response and to a compromised blood-brain barrier possibly due to disrupted cell-cell and cell-extracellular matrix interactions. The results also suggest that antihyperlipidaemic therapy may contribute to lowering risk for white matter hyperintensities possibly through protection against blood-brain barrier disruption.

Increased chromatin accessibility facilitates intron retention in specific cell differentiation states.

Dynamic intron retention (IR) in vertebrate cells is of widespread biological importance. Aberrant IR is associated with numerous human diseases including several cancers. Despite consistent reports demonstrating that intrinsic sequence features can help introns evade splicing, conflicting findings about cell type- or condition-specific IR regulation by trans-regulatory and epigenetic mechanisms demand an unbiased and systematic analysis of IR in a controlled experimental setting. We integrated matched mRNA sequencing (mRNA-Seq), whole-genome bisulfite sequencing (WGBS), nucleosome occupancy methylome sequencing (NOMe-Seq) and chromatin immunoprecipitation sequencing (ChIP-Seq) data from primary human myeloid and lymphoid cells. Using these multi-omics data and machine learning, we trained two complementary models to determine the role of epigenetic factors in the regulation of IR in cells of the innate immune system. We show that increased chromatin accessibility, as revealed by nucleosome-free regions, contributes substantially to the retention of introns in a cell-specific manner. We also confirm that intrinsic characteristics of introns are key for them to evade splicing. This study suggests an important role for chromatin architecture in IR regulation. With an increasing appreciation that pathogenic alterations are linked to RNA processing, our findings may provide useful insights for the development of novel therapeutic approaches that target aberrant splicing.

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Genome-wide meta-analyses reveal novel loci for verbal short-term memory and learning.

Understanding the genomic basis of memory processes may help in combating neurodegenerative disorders. Hence, we examined the associations of common genetic variants with verbal short-term memory and verbal learning in adults without dementia or stroke (N = 53,637). We identified novel loci in the intronic region of CDH18, and at 13q21 and 3p21.1, as well as an expected signal in the APOE/APOC1/TOMM40 region. These results replicated in an independent sample. Functional and bioinformatic analyses supported many of these loci and further implicated POC1. We showed that polygenic score for verbal learning associated with brain activation in right parieto-occipital region during working memory task. Finally, we showed genetic correlations of these memory traits with several neurocognitive and health outcomes. Our findings suggest a role of several genomic loci in verbal memory processes.

The immune-related circRNA-miRNA-mRNA ceRNA regulatory network in the liver of turbot (Scophthalmus maximus L.) induced by Vibrio anguillarum.

Recently, Vibrio anguillarum, a Gram-negative pathogenic bacterium, has been becoming a major constraint on the development of the turbot aquaculture industry because of its characteristics of worldwide distribution, broad host range and potentially devastating impacts. Although the functions of protein-coding mRNAs in the immune response against bacterial infection have been reported, as well as several non-coding RNAs (ncRNAs), such as circular RNAs (circRNAs) and microRNAs (miRNAs), the relationships between mRNAs and ncRNAs in the immune system of turbot liver are still limited during bacterial infection. In present study, the comprehensive analyses of whole-transcriptome sequencing were conducted in turbot liver infected by V. anguillarum. The differential expression was analyzed in the data of circRNAs, miRNAs, and mRNAs. The interactions of miRNA-circRNA pairs and miRNA-mRNA pairs were predicted basing on the negative regulatory relationships between miRNAs and their target circRNAs\mRNAs. The circRNA-related ceRNA regulatory networks were constructed for the analyses of regulated mechanism in turbot immune system. Subsequently, the RT-qPCR was carried out to verify the results of sequencing. Finally, we identified 31 circRNAs, 53 miRNAs and 948 mRNAs with differential expression. Gene set enrichment analyses using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways showed that innate immunity was principally activated at the early stages of infection, while adaptive immunity was activated after 24 h. Finally, 65 circRNA-miRNA-mRNA pathways were constructed, based on the hypothesis of ceRNA regulatory networks. In conclusion, our findings provide new insights on the underlying immune response to bacterial infection and identify novel target genes for the prevention and control of disease in turbot.

Plasma glial fibrillary acidic protein in autosomal dominant Alzheimer's disease: Associations with Aß-PET, neurodegeneration, and cognition.

BACKGROUND: Glial fibrillary acidic protein (GFAP) is a promising candidate blood-based biomarker for Alzheimer's disease (AD) diagnosis and prognostication. The timing of its disease-associated changes, its clinical correlates, and biofluid-type dependency will influence its clinical utility. METHODS: We evaluated plasma, serum, and cerebrospinal fluid (CSF) GFAP in families with autosomal dominant AD (ADAD), leveraging the predictable age at symptom onset to determine changes by stage of disease. RESULTS: Plasma GFAP elevations appear a decade before expected symptom onset, after amyloid beta (Aß) accumulation and prior to neurodegeneration and cognitive decline. Plasma GFAP distinguished Aß-positive from Aß-negative ADAD participants and showed a stronger relationship with Aß load in asymptomatic than symptomatic ADAD. Higher plasma GFAP was associated with the degree and rate of neurodegeneration and cognitive impairment. Serum GFAP showed similar relationships, but these were less pronounced for CSF GFAP. CONCLUSION: Our findings support a role for plasma GFAP as a clinical biomarker of Aß-related astrocyte reactivity that is associated with cognitive decline and neurodegeneration. HIGHLIGHTS: Plasma glial fibrillary acidic protein (GFAP) elevations appear a decade before expected symptom onset in autosomal dominant Alzheimer's disease (ADAD). Plasma GFAP was associated to amyloid positivity in asymptomatic ADAD. Plasma GFAP increased with clinical severity and predicted disease progression. Plasma and serum GFAP carried similar information in ADAD, while cerebrospinal fluid GFAP did not.

A systematic literature review of evidence for the use of assistive exoskeletons in defence and security use cases.

Advances in assistive exoskeleton technology, and a boom in related scientific literature, prompted a need to review the potential use of exoskeletons in defence and security. A systematic review examined the evidence for successful augmentation of human performance in activities deemed most relevant to military tasks. Categories of activities were determined a priori through literature scoping and Human Factors workshops with military stakeholders. Workshops identified promising opportunities and risks for integration of exoskeletons into military use cases. The review revealed promising evidence for exoskeletons' capacity to assist with load carriage, manual lifting, and working with tools. However, the review also revealed significant gaps in exoskeleton capabilities and likely performance levels required in the use case scenarios. Consequently, it was recommended that a future roadmap for introducing exoskeletons to military environments requires development of performance criteria for exoskeletons that can be used to implement a human-centred approach to research and development.

We assessed the state-of-the-art for the use of wearable assistive exoskeletons in UK defence and security use cases. A full systematic review of the literature was undertaken, informed by use cases developed in military stakeholder workshops. Clear gaps in exoskeleton capability and use case requirements were identified, leading to recommendations for future work.

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.

Epigenome-wide meta-analysis of blood DNA methylation and its association with subcortical volumes: findings from the ENIGMA Epigenetics Working Group.

DNA methylation, which is modulated by both genetic factors and environmental exposures, may offer a unique opportunity to discover novel biomarkers of disease-related brain phenotypes, even when measured in other tissues than brain, such as blood. A few studies of small sample sizes have revealed associations between blood DNA methylation and neuropsychopathology, however, large-scale epigenome-wide association studies (EWAS) are needed to investigate the utility of DNA methylation profiling as a peripheral marker for the brain. Here, in an analysis of eleven international cohorts, totalling 3337 individuals, we report epigenome-wide meta-analyses of blood DNA methylation with volumes of the hippocampus, thalamus and nucleus accumbens (NAcc)-three subcortical regions selected for their associations with disease and heritability and volumetric variability. Analyses of individual CpGs revealed genome-wide significant associations with hippocampal volume at two loci. No significant associations were found for analyses of thalamus and nucleus accumbens volumes. Cluster-based analyses revealed additional differentially methylated regions (DMRs) associated with hippocampal volume. DNA methylation at these loci affected expression of proximal genes involved in learning and memory, stem cell maintenance and differentiation, fatty acid metabolism and type-2 diabetes. These DNA methylation marks, their interaction with genetic variants and their impact on gene expression offer new insights into the relationship between epigenetic variation and brain structure and may provide the basis for biomarker discovery in neurodegeneration and neuropsychiatric conditions.

Systematic identification and characterization of lncRNAs and lncRNA-miRNA-mRNA networks in the liver of turbot (Scophthalmus maximus L.) induced with Vibrio anguillarum.

Long noncoding RNAs (lncRNAs), can regulate mRNA by targeting miRNA in a competing endogenous RNA network, have become a hot topic in the research of fish immune mechanism recent years. While in turbot (Scophthalmus maximus L.), an economically important marine fish, there are limited researches about the role of lncRNAs in its immune response to bacterial infection. In this study, a total of 184 differentially expressed lncRNAs (DElncRNAs) were systematically identified and characterized using whole-transcriptome sequencing of the liver of turbot challenged with Vibrioanguillarum at 0 h (control) and three different time points post infection (2 h, 12 h and 24 h, respectively). Subsequently, GO and KEGG signaling pathways of differentially expressed lncRNAs were analyzed to predict their function. We found that lncRNAs in our results were significantly enriched in several immune-related signaling pathways, including the NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, Cytokine-cytokine receptor, MAPK signaling pathway, phagosome, PPAR signaling pathway and the regulation of autophagy. In addition, a total of 492 DE lncRNA - DE miRNA -DE mRNA networks were identified at three different time points post infection, which were consisted of 102 networks at 2 h, 122 networks at 12 h and 81 networks at 24 h post infection, respectively. Noticeably, 92 of these regulated networks were immune-related. These observations suggested that lncRNAs can regulate the expression of immune-related genes in the response to bacterial infection in turbot. Moreover, our findings would provide a new insight into the immune response of turbot to pathogen infection and lay a foundation for future study.

Diagnostic and prognostic plasma biomarkers for preclinical Alzheimer's disease.

INTRODUCTION: This study involved a parallel comparison of the diagnostic and longitudinal monitoring potential of plasma glial fibrillary acidic protein (GFAP), total tau (t-tau), phosphorylated tau (p-tau181 and p-tau231), and neurofilament light (NFL) in preclinical Alzheimer's disease (AD). METHODS: Plasma proteins were measured using Simoa assays in cognitively unimpaired older adults (CU), with either absence (Aß-) or presence (Aß+) of brain amyloidosis. RESULTS: Plasma GFAP, t-tau, p-tau181, and p-tau231 concentrations were higher in Aß+ CU compared with Aß- CU cross-sectionally. GFAP had the highest effect size and area under the curve (AUC) in differentiating between Aß+ and Aß- CU; however, no statistically significant differences were observed between the AUCs of GFAP, p-tau181, and p-tau231, but all were significantly higher than the AUC of NFL, and the AUC of GFAP was higher than the AUC of t-tau. The combination of a base model (BM), comprising the AD risk factors, age, sex, and apolipoprotein E gene (APOE) ε4 status with GFAP was observed to have a higher AUC (>90%) compared with the combination of BM with any of the other proteins investigated in the current study. Longitudinal analyses showed increased GFAP and p-tau181 in Aß+ CU and increased NFL in Aß- CU, over a 12-month duration. GFAP, p-tau181, p-tau231, and NFL showed significant correlations with cognition, whereas no significant correlations were observed with hippocampal volume. DISCUSSION: These findings highlight the diagnostic and longitudinal monitoring potential of GFAP and p-tau for preclinical AD.

Enduring epigenetic landmarks define the cancer microenvironment.

The growth and progression of solid tumors involves dynamic cross-talk between cancer epithelium and the surrounding microenvironment. To date, molecular profiling has largely been restricted to the epithelial component of tumors; therefore, features underpinning the persistent protumorigenic phenotype of the tumor microenvironment are unknown. Using whole-genome bisulfite sequencing, we show for the first time that cancer-associated fibroblasts (CAFs) from localized prostate cancer display remarkably distinct and enduring genome-wide changes in DNA methylation, significantly at enhancers and promoters, compared to nonmalignant prostate fibroblasts (NPFs). Differentially methylated regions associated with changes in gene expression have cancer-related functions and accurately distinguish CAFs from NPFs. Remarkably, a subset of changes is shared with prostate cancer epithelial cells, revealing the new concept of tumor-specific epigenome modifications in the tumor and its microenvironment. The distinct methylome of CAFs provides a novel epigenetic hallmark of the cancer microenvironment and promises new biomarkers to improve interpretation of diagnostic samples.

Correction: Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Prior to and following the publication of this article the authors noted that the complete list of authors was not included in the main article and was only present in Supplementary Table 1. The author list in the original article has now been updated to include all authors, and Supplementary Table 1 has been removed. All other supplementary files have now been updated accordingly. Furthermore, in Table 1 of this Article, the replication cohort for the row Close relative in data set, n (%) was incorrect. All values have now been corrected to 0(0%). The publishers would like to apologise for this error and the inconvenience it may have caused.

Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia.

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (ß = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (ß = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10-6, 1.7 × 10-9, 3.5 × 10-12 and 1.0 × 10-4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.

Accounting for body mass effects in the estimation of field metabolic rates from body acceleration.

Dynamic body acceleration (DBA), measured through animal-attached tags, has emerged as a powerful method for estimating field metabolic rates of free-ranging individuals. Following respirometry to calibrate oxygen consumption rate (MO2) with DBA under controlled conditions, predictive models can be applied to DBA data collected from free-ranging individuals. However, laboratory calibrations are generally performed on a relatively narrow size range of animals, which may introduce biases if predictive models are applied to differently sized individuals in the field. Here, we tested the mass dependence of the MO2-DBA relationship to develop an experimental framework for the estimation of field metabolic rates when organisms differ in size. We performed respirometry experiments with individuals spanning one order of magnitude in body mass (1.74-17.15 kg) and used a two-stage modelling process to assess the intraspecific scale dependence of the MO2-DBA relationship and incorporate such dependencies into the coefficients of MO2 predictive models. The final predictive model showed scale dependence; the slope of the MO2-DBA relationship was strongly allometric (M1.55), whereas the intercept term scaled closer to isometry (M1.08). Using bootstrapping and simulations, we evaluated the performance of this coefficient-corrected model against commonly used methods of accounting for mass effects on the MO2-DBA relationship and found the lowest error and bias in the coefficient-corrected approach. The strong scale dependence of the MO2-DBA relationship indicates that caution must be exercised when models developed using one size class are applied to individuals of different sizes.

Common genetic variants influence human subcortical brain structures.

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume and intracranial volume. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10(-33); 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

Global and Regional Development of the Human Cerebral Cortex: Molecular Architecture and Occupational Aptitudes.

We have carried out meta-analyses of genome-wide association studies (GWAS) (n = 23 784) of the first two principal components (PCs) that group together cortical regions with shared variance in their surface area. PC1 (global) captured variations of most regions, whereas PC2 (visual) was specific to the primary and secondary visual cortices. We identified a total of 18 (PC1) and 17 (PC2) independent loci, which were replicated in another 25 746 individuals. The loci of the global PC1 included those associated previously with intracranial volume and/or general cognitive function, such as MAPT and IGF2BP1. The loci of the visual PC2 included DAAM1, a key player in the planar-cell-polarity pathway. We then tested associations with occupational aptitudes and, as predicted, found that the global PC1 was associated with General Learning Ability, and the visual PC2 was associated with the Form Perception aptitude. These results suggest that interindividual variations in global and regional development of the human cerebral cortex (and its molecular architecture) cascade-albeit in a very limited manner-to behaviors as complex as the choice of one's occupation.

Changes in dietary fat intake and associations with mental health in a UK public sample during the COVID-19 pandemic.

BACKGROUND: Consumption of unhealthy foods may have changed during the COVID-19 pandemic. This study explored how dietary fat intake was impacted in a sample of the UK public who were social distancing during the COVID-19 pandemic. METHODS: Data were collected from a UK COVID-19 online survey. Fat intake was measured using the Dietary Instrument for Nutrition Education questionnaire. Anxiety and depressive symptoms were assessed using Becks' Anxiety and Depression Inventories, while the short-form Warwick-Edinburgh Mental Well-being Scale assessed mental well-being. Differences between individuals who increased versus decreased fat intake were explored using chi-square or independent sample t-tests. Association between fat intake and mental health was explored using adjusted linear regression models. RESULTS: Eight hundred and eighty-seven adults were included. Approximately, 34% recorded medium-to-high levels of fat consumption during social distancing. Around 48% reported decreased fat intake during social distancing compared to usual levels, while 41.3% documented increased fat intake. Fat intake was not significantly associated (P > 0.05) with any measures of mental health. CONCLUSIONS: A higher proportion of a sample of UK adults social distancing during the COVID-19 pandemic recorded decreased fat intake when compared to levels prior to social distancing. There appeared to be no associations between fat intake and mental health.

Plasma secretory phospholipase A2 as an early marker for late-onset sepsis in preterm infants-a pilot study.

Preterm infants are particularly susceptible to bacterial late-onset sepsis (LOS). Diagnosis by blood culture and inflammatory markers have sub-optimal sensitivity and specificity and prolonged reporting times. There is an urgent need for more rapid, accurate adjunctive diagnostics in LOS to improve management and minimise antibiotic exposure. We measured the diagnostic performance of secretory phospholipase A2 type IIA (sPLA2-IIA) in very preterm infants (<30 weeks gestational age) with suspected LOS. Plasma sPLA2-IIA levels were elevated in infants with LOS (n = 28) compared to those without LOS (n = 21; median 30,970 vs. 2534 pg/ml, p < 0.0001). The mean area under the curve was 0.884 (95% CI: 0.771, 0.977) with a sensitivity of 0.907 (95% CI: 0.667, 1.00) and specificity of 0.804 (95% CI: 0.600, 1.00). The positive and negative predictive values were 0.833 (95% CI: 0.664, 0.927) and 0.842 (95% CI: 0.624, 0.945), respectively. This pilot study suggests that sPLA2-IIA may have clinical utility for the early diagnosis of LOS in very preterm infants, potentially informing clinical management and antibiotic stewardship.

Wearable Devices Suitable for Monitoring Twenty Four Hour Heart Rate Variability in Military Populations.

Heart rate variability (HRV) measurements provide information on the autonomic nervous system and the balance between parasympathetic and sympathetic activity. A high HRV can be advantageous, reflecting the ability of the autonomic nervous system to adapt, whereas a low HRV can be indicative of fatigue, overtraining or health issues. There has been a surge in wearable devices that claim to measure HRV. Some of these include spot measurements, whilst others only record during periods of rest and/or sleep. Few are capable of continuously measuring HRV (≥24 h). We undertook a narrative review of the literature with the aim to determine which currently available wearable devices are capable of measuring continuous, precise HRV measures. The review also aims to evaluate which devices would be suitable in a field setting specific to military populations. The Polar H10 appears to be the most accurate wearable device when compared to criterion measures and even appears to supersede traditional methods during exercise. However, currently, the H10 must be paired with a watch to enable the raw data to be extracted for HRV analysis if users need to avoid using an app (for security or data ownership reasons) which incurs additional cost.