The Mg/Ca–temperature relationship in brachiopod shells: calibrating a potential palaeoseasonality proxy

Brachiopods are long-lived, long-ranging, extant organisms, of which some groups precipitate a relatively diagenetically stable low magnesium calcite shell. Previous work has suggested that the incorporation of Mg into brachiopod calcite may be controlled by temperature (Brand et al., 2013). Here we build upon this work by using laser ablation sampling to define the intra-shell variations in two modern brachiopod species,Terebratulina retusa (Linnaeus, 1758) and Liothyrella neozelanica (Thomson, 1918). We studied three T. retusa shells collected live from the Firth of Lorne, Scotland, which witnessed annual temperature variations on the order of 7 °C, in addition to four L. neozelanica shells, which were dredged from a water depth transect (168–1488 m) off the north coast of New Zealand. The comparison of intra-shell Mg/Ca profiles with shell δ<sup>18</sup>O confirms a temperature control on brachiopod Mg/Ca and supports the use of brachiopod Mg/Ca as a palaeoseasonality indicator. Our preliminary temperature calibrations are Mg/Ca = 1.76 ± 0.27 e<sup>(0.16 ± 0.03)T</sup>, R<sup>2</sup> = 0.75, for T. retusa and Mg/Ca = 0.49 ± 1.27 e<sup>(0.2 ± 0.11)T</sup>, R<sup>2</sup> = 0.32, for L. neozelanica (errors are 95% confidence intervals)

Processing liquid metal for conformable electronics

Future generations of robots, electronics, and assistive medical devices will include systems that are soft, elastically deformable, and may adapt their functionality in unstructured environments. This will require soft active materials for power circuits and sensing of deformation and contact pressure. Liquid-embedded elastomer electronics offer one solution as key elements of highly deformable and soft robotic systems. Several designs for stretchable conductors and soft sensory skins (including strain, pressure, and curvature sensors) based on a liquid-embedded-elastomer approach have been developed. Many of these fluid–elastomer composites utilize liquid metal alloys due to their high conductivities and inherent compliance. Understanding how these alloys can be processed for high-yield manufacturability is critical to the development of parallel processing technology, which is needed to create more complex and low-cost systems. This discussion will highlight surface interactions between droplets of gallium–indium alloys and elastomeric substrates, and the implementation of this study to selective patterning, direct-writing, and inkjet printing of hyperelastic electronic components

Testing the effect of carbonate saturation on the Sr/Ca of biogenic aragonite: A case study from the River Ehen, Cumbria, UK

It has been suggested that the incorporation of strontium into biogenic aragonite may be influenced by the degree of carbonate saturation in aquatic environments. We measured the Sr/Ca ratios of river water and the aragonitic shells of freshwater bivalves (Margaritifera margaritifera) from two sites with different carbonate saturation states in the River Ehen, Cumbria, UK. Shell Sr/Ca and river water Sr/Ca are 0.1 mmol/mol and 0.42 mmol/mol lower, respectively, at the high carbonate saturation site. However, the distribution coefficients of strontium into aragonite (KD) are the same (∼0.28) at both sites. These analyses show that Sr uptake into aragonite bivalve shells is not affected by the degree of carbonate saturation of the water, perhaps reflecting a strong biological control on trace element incorporation

Reduced Cognitive Assessment Scores Among Individuals With Magnetic Resonance Imaging-Detected Vascular Brain Injury

Background and Purpose- Little is known about the association between covert vascular brain injury and cognitive impairment in middle-aged populations. We investigated if scores on a cognitive screen were lower in individuals with higher cardiovascular risk, and those with covert vascular brain injury. Methods- Seven thousand five hundred forty-seven adults, aged 35 to 69 years, free of cardiovascular disease underwent a cognitive assessment using the Digital Symbol Substitution test and Montreal Cognitive Assessment, and magnetic resonance imaging (MRI) to detect covert vascular brain injury (high white matter hyperintensities, lacunar, and nonlacunar brain infarctions). Cardiovascular risk factors were quantified using the INTERHEART (A Global Study of Risk Factors for Acute Myocardial Infarction) risk score. Multivariable mixed models tested for independent determinants of reduced cognitive scores. The population attributable risk of risk factors and MRI vascular brain injury on low cognitive scores was calculated. Results- The mean age of participants was 58 (SD, 9) years; 55% were women. Montreal Cognitive Assessment and Digital Symbol Substitution test scores decreased significantly with increasing age

Cardiovascular risk scoring and magnetic resonance imaging detected subclinical cerebrovascular disease

AIMS: Cardiovascular risk factors are used for risk stratification in primary prevention. We sought to determine if simple cardiac risk scores are associated with magnetic resonance imaging (MRI)-detected subclinical cerebrovascular disease including carotid wall volume (CWV), carotid intraplaque haemorrhage (IPH), and silent brain infarction (SBI). METHODS AND RESULTS: A total of 7594 adults with no history of cardiovascular disease (CVD) underwent risk factor assessment and a non-contrast enhanced MRI of the carotid arteries and brain using a standardized protocol in a population-based cohort recruited between 2014 and 2018. The non-lab-based INTERHEART risk score (IHRS) was calculated in all participants; the Framingham Risk Score was calculated in a subset who provided blood samples (n = 3889). The association between these risk scores and MRI measures of CWV, carotid IPH, and SBI was determined. The mean age of the cohort was 58 (8.9) years, 55% were women. Each 5-point increase (∼1 SD) in the IHRS was associated with a 9 mm3 increase in CWV, adjusted for sex (P \u3c 0.0001), a 23% increase in IPH [95% confidence interval (CI) 9-38%], and a 32% (95% CI 20-45%) increase in SBI. These associations were consistent for lacunar and non-lacunar brain infarction. The Framingham Risk Score was also significantly associated with CWV, IPH, and SBI. CWV was additive and independent to the risk scores in its association with IPH and SBI. CONCLUSION: Simple cardiovascular risk scores are significantly associated with the presence of MRI-detected subclinical cerebrovascular disease, including CWV, IPH, and SBI in an adult population without known clinical CVD

Relative sea-level rise around East Antarctica during Oligocene glaciation

During the middle and late Eocene (∼48-34 Myr ago), the Earth's climate cooled and an ice sheet built up on Antarctica. The stepwise expansion of ice on Antarcticainduced crustal deformation and gravitational perturbations around the continent. Close to the ice sheet, sea level rosedespite an overall reduction in the mass of the ocean caused by the transfer of water to the ice sheet. Here we identify the crustal response to ice-sheet growth by forcing a glacial-hydro isostatic adjustment model with an Antarctic ice-sheet model. We find that the shelf areas around East Antarctica first shoaled as upper mantle material upwelled and a peripheral forebulge developed. The inner shelf subsequently subsided as lithosphere flexure extended outwards from the ice-sheet margins. Consequently the coasts experienced a progressive relative sea-level rise. Our analysis of sediment cores from the vicinity of the Antarctic ice sheet are in agreement with the spatial patterns of relative sea-level change indicated by our simulations. Our results are consistent with the suggestion that near-field processes such as local sea-level change influence the equilibrium state obtained by an icesheet grounding line

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.JW is supported by a Cancer Research UK Cambridge Cancer Centre Clinical Research Training Fellowship. Funding for the NIHR BioResource – Rare diseases project was provided by the National Institute for Health Research (NIHR, grant number RG65966). ERM acknowledges support from the European Research Council (Advanced Researcher Award), NIHR (Senior Investigator Award and Cambridge NIHR Biomedical Research Centre), Cancer Research UK Cambridge Cancer Centre and Medical Research Council Infrastructure Award. The University of Cambridge has received salary support in respect of EM from the NHS in the East of England through the Clinical Academic Reserve. The views expressed are those of the authors and not necessarily those of the NHS or Department of Health. DGE is an NIHR Senior Investigator and is supported by the all Manchester NIHR Biomedical Research Centre

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Liquid metal particle popping: Nanoscale to macroscale

Liquid metal nanoparticles can be used to produce stretchable electronic devices. Understanding the mechanical properties of liquid metal nanoparticles is crucial to optimizing their use in various applications, especially printing of flexible, stretchable electronics. Smaller nanoparticles are desired for high-resolution printing and compatibility with existing scalable manufacturing methods; however, they contain less liquid metal and are more difficult to rupture than larger particles, making them less desirable for post-processing functionality. This study investigates the mechanics of liquid metal particle rupture as a function of particle size. We employ compression of particle films to characterize the composition of the particle core and derive a minimum particle size required to achieve sintering and subsequent conductance. We further derive the force required to rupture a single particle and validate the results by rupturing individual nanoparticles using atomic force microscopy. In addition, we relate the liquid metal nanoparticles to isotropically-elastic thin-shell microspheres to approximate the particle shell stiffness. Using the results from this study, spray printing has been used as a scalable process that permits the printing of larger particles in high resolution patterns. Furthermore, existent sintering methods are developed, specifically using laser systems, high voltage generators, and exposure to extreme temperatures. An increased understanding of the behavior of liquid metal nanoparticles during rupture reveals limitations of current manufacturing processes and paves the way for the next generation of scalable mass-producible soft electronics using additive manufacturing technologies