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In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.

Background: Blueberry muffin is a descriptive term for a neonate with multiple purpuric skin lesions. Many causes are known, amongst them life-threatening diseases like congenital infections or leukemia. Indeterminate cell histiocytosis (ICH) is an exceptionally rare cause of blueberry muffin rash. ICH is a histiocytic disorder which can be limited to the skin or can present with systemic involvement. A mutation that has been described in histiocytic disorders is a MAP2K1 mutation. In ICH, this mutation has previously been described in merely one case. Case presentation: A term male neonate was admitted to the neonatology ward directly after birth because of a blueberry muffin rash. ICH was diagnosed on skin biopsy. The lesions resolved spontaneously. The patient is currently 3 years old and has had no cutaneous lesions or systemic involvement so far. This disease course is similar to that of the Hashimoto-Pritzker variant of LCH. Conclusions: ICH can manifest in neonates as resolving skin lesions. It is limited to the skin in most cases, but systemic development is possible. Therefore, it is essential to confirm the diagnosis with a biopsy before the lesions resolve and to monitor these patients closely with routine follow-up.

In the current article the aims for a constructive way forward in Drug-Induced Liver Injury (DILI) are to highlight the most important priorities in research and clinical science, therefore supporting a more informed, focused, and better funded future for European DILI research. This Roadmap aims to identify key challenges, define a shared vision across all stakeholders for the opportunities to overcome these challenges and propose a high-quality research program to achieve progress on the prediction, prevention, diagnosis and management of this condition and impact on healthcare practice in the field of DILI. This will involve 1. Creation of a database encompassing optimised case report form for prospectively identified DILI cases with well-characterised controls with competing diagnoses, biological samples, and imaging data; 2. Establishing of preclinical models to improve the assessment and prediction of hepatotoxicity in humans to guide future drug safety testing; 3. Emphasis on implementation science and 4. Enhanced collaboration between drug-developers, clinicians and regulatory scientists. This proposed operational framework will advance DILI research and may bring together basic, applied, translational and clinical research in DILI.

Inferences on the early evolution of the Earth's mantle can be deduced from long-lived radiogenic isotope Lu-176-Hf-176 and systems such as Sm-147-Nd-143, for which both parent and daughter elements largely remain immobile at low metamorphic grades. However, it remains ambiguous when and to what extent mantle-crust differentiation processes had started in the Archean. For a better understanding of Archean mantle-crust evolution, we determined the initial Lu-176-Hf-176, Sm-147-Nd-143, and, in a new approach, the La-138-Ce-138 isotope compositions of a suite of Archean mafic-ultramafic rock samples from the 3.53-2.83 Ga old Pilbara Craton and 2.78-2.63 Ga old Fortescue Group in NW Australia. These rocks represent one of the best-preserved Archean successions worldwide and contain mafic-ultramafic rocks that were erupted during repeated and long-lived pulses of volcanism throughout much of the Archean. Mantlederived mafic-ultramafic rock samples were collected from six major stratigraphic groups of the Pilbara Craton and the overlying Fortescue Group in order to characterize the parental mantle source regions of the lavas and to reconstruct the temporal evolution of the ambient mantle beneath this piece of cratonic lithosphere. In addition, we analyzed contemporaneous TTG-like igneous suites and interbedded sediments in order to reconstruct the lithospheric evolution of the Pilbara Craton. The Hf-Nd-Ce isotope data imply the onset of mantle-crust differentiation in the Pilbara Craton as early as similar to 4.2 Ga, well prior to any of the preserved stratigraphy. Within error, coupled Ce-Nd-Hf isotope arrays all intersect chondritic values, implying that the Earth is of broadly chondritic composition, also for the La-138-Ce-138 isotope system. Mafic rocks usually yield strongly coupled epsilon Hf-(i), epsilon Nd-(i) and epsilon Ce-(i) values that form a mixing line between an evolving depleted upper mantle composition and the primitive mantle value (epsilon Hf-(i) ca. 0

The Eoarchean (> 3600 Ma, or millions of years ago) folded and metamorphosed Isua supracrustal belt and the adjacent orthogneiss exposures of Greenland contain rare low deformation lenses that display some uniquelypreserved components of Earth's oldest rock record. These include world's oldest (but contested) stromatolites in dolomitic carbonates, conglomerates, pillow basalts demonstrating submarine eruption, slivers of upper mantle rocks, formation of earliest continental crust by multistage tonalite + diorite emplacement followed by intracrustal granite production. All these diverse occurrences are keys to establish early Earth's processes at the start of the geological record. Although some of these features are preserved at several localities, other critical ones are exposed on only a few m2 of rock at single localities or are of historical significance. None of these sites are currently protected, and there is a reliance on responsible sampling to keep them intact for future generations. Given the high interest in the Archean Eon, combined with the increased ease of fieldwork in remote localities, many significant 'Deep Time' localities in not only Greenland but worldwide are in danger of eradication. Here, five key Isua area geological sites are presented, with an explanation of their significance and worthiness for initially reliance on already-collected samples, but hopefully ultimately government protection. This highlights an increasing problem of destruction of in situ evidence of Earth's unique early geological heritage and the need for collaboration in protecting and archiving of these key scientific resources.

The ∼3700 Ma and 3800 Ma meta-volcanic and -sedimentary rocks in the Isua supracrustal belt (Greenland) were affected by heterogeneous ductile deformation under amphibolite facies conditions (∼500–650 °C), and variably modified by secondary silica and carbonate mineralisation deposited from diagenetic and metasomatic fluids. Rare low-deformation areas preserve original volcanic features – submarine basaltic pillows and sedimentary features – including bedding. These are best-preserved in two dimensions on flat- to moderately-inclined outcrop surfaces, but invariably are tectonically-stretched along a steeply-plunging third dimension, through stretching in the direction of fold axes; a style of deformation found throughout Earth’s history. There is a debate about whether rare relicts of ∼3700 Ma stromatolites preserved in metadolomites that formed in a shallow marine setting (Nutman et al., 2016) represent bona fide biogenic primary structures fortuitously preserved in low deformation, or whether these structures are manifestations of deformation combined with non-biogenic deposition of secondary carbonate (Allwood et al., 2018). Here, we critically test the primary nature of the sedimentary rocks hosting the proposed stromatolites and also the veracity of the proposed stromatolites, by addressing the following questions: (i) Are the rocks an in situ outcrop of known age, or displaced blocks of unknown age or origin?; (ii) How much of the carbonate is of an originally sedimentary versus a secondary (i.e., metasomatic – introduced) origin?; (iii) Is the seawater-like REE + Y (rare earth element and yttrium) trace element signature carried definitely by carbonate minerals and therefore diagnostic of a cool, surficial sedimentary system?; (iv) Are the proposed stromatolites consistent with biogenicity in terms of their geometry and fine-scale layering, or could they be the product of soft sediment or structural deformation (compression in folding)? The answers to these

Executive summary provided in lieu of abstract., SCOPUS: no.j, info:eu-repo/semantics/published

Crystallography has a long history of providing knowledge and methods for applications in other disciplines. The identification of minerals using X-ray diffraction is one of the most important contributions of crystallography to earth sciences. However, when the crystal itself has been dissolved, replaced or deeply modified during the geological history of the rocks, diffraction information is not available. Instead, the morphology of the crystal cast provides the only crystallographic information on the original mineral phase and the environment of crystal growth. This article reports an investigation of crystal pseudomorphs and crystal casts found in a carbonate-chert facies from the 3.48 Ga-old Dresser Formation (Pilbara Craton, Australia), considered to host some of the oldest remnants of life. A combination of X-ray microtomography, energy-dispersive X-ray spectroscopy and crystallographic methods has been used to reveal the original phases of these Archean pseudomorphs. It is found with a high degree of confidence that the original crystals forming in Archean times were hollow aragonite, the high-temperature polymorphs of calcium carbonate, rather than other possible alternatives such as gypsum (CaSO·2H0) and nahcolite (NaHCO). The methodology used is described in detail.

© 2018 The Author(s). The Great Oxidation Event (GOE) has been defined as the time interval when sufficient atmospheric oxygen accumulated to prevent the generation and preservation of mass-independent fractionation of sulphur isotopes (MIF-S) in sedimentary rocks. Existing correlations suggest that the GOE was rapid and globally synchronous. Here we apply sulphur isotope analysis of diagenetic sulphides combined with U-Pb and Re-Os geochronology to document the sulphur cycle evolution in Western Australia spanning the GOE. Our data indicate that, from ~2.45 Gyr to beyond 2.31 Gyr, MIF-S was preserved in sulphides punctuated by several episodes of MIF-S disappearance. These results establish the MIF-S record as asynchronous between South Africa, North America and Australia, argue for regional-scale modulation of MIF-S memory effects due to oxidative weathering after the onset of the GOE, and suggest that the current paradigm of placing the GOE at 2.33-2.32 Ga based on the last occurrence of MIF-S in South Africa should be re-evaluated.

The significance of oxygen isotope ratios in Archean chert has long been debated. Cherts from the c. 3.4 Ga Strelley Pool Formation (SPF) (Pilbara Craton, Western Australia) host some of the oldest stromatolite and microfossil evidence for life, but the genesis and timing of silica cements has been unclear. Field relations, petrography and a combination of laser fluorination and in-situ SIMS measurements of d 18 O in quartz show that bedded cherts of the SPF were originally precipitated as carbonates and were later widely replaced by quartz. Three localities were studied and analyzed for d 18 O(Qz) in chert: 1) Camel Creek: foliated, metamorphosed, bedded cherts and meter-scale black chert veins; 2) Unconformity Ridge and ABDP8 drill core: stromatolitic and bedded chert overlying basal detrital quartz sandstone; and 3) the Trendall locality: “bedded” stromatolitic chert replacing original dolomite, low temperature hydrothermal quartz, and mm- to decimeter-scale chert-quartz veins. Laser fluorination (mm-scale) values of d 18 O(Qz) range from: 14.2 to 18.2‰ VSMOW at Camel Creek; 9.3 to 18.9‰ at Unconformity Ridge; and 13.7 to 25.7‰ at Trendall. Values of d 18 O(Qz) in cm to decimeter-scale hydrothermal chert veins cutting bedded carbonates at Trendall range from ca. 15 to 16‰, whereas “bedded cherts” are 17 to 26‰. These laser data include the highest d 18 O values reported for cherts in Paleoarchean sediments and are up to 4‰ higher than the upper limit of ~22‰ reported in other studies, in apparent contrast to the long-standing secular-temporal trend which shows such high d 18 O only in younger chert. However, analysis by laser fluorination at the 1-mm scale cannot resolve microtextures seen petrographically. In contrast, in-situ SIMS analyses can resolve petrographic microtextures and show d 18 O(Qz) at 10-µm scale have an even greater range of 7–31‰ in “bedded” cherts at the Trendall locality, up to 9‰ above the secular-temporal trend. Textures observed optically