The Late Quaternary sediment successions of Llangorse Lake, south Wales

The last British-Irish Ice Sheet (BIIS) created a landscape with many sedimentary basins that preserve archives of paleoenvironmental and paleoclimatic change during the Last Glacial-Interglacial Transition (LGIT; ~ 18-8 ka BP). The typical lithostratigraphic succession of these archives is composed of minerogenic/allogenic sediments formed during cold climatic conditions and organic-rich/authigenic sediments during warmer climates. This paper presents a multi-core lithostratigraphy compiled from the extant lake and surrounding basin at Llangorse Lake, south Wales, a basin lying within the southernmost limits of the last BIIS. This lake contains one of the longest continuous terrestrial sediment successions in the UK. Uncertainty previously existed concerning the presence and distribution of sediments at the site related to the Windermere Interstadial (~ 14.7 to ~ 12.9 ka BP) and Loch Lomond Stadial (~ 12.9 to 11.7 ka BP). A new borehole survey demonstrates that LGIT-age sediments are present at the site with nekron mud (gyttja), corresponding to the Lateglacial Interstadial, deposited in the deeper part of the lake waters and that these deposits are equivalent in age to marl deposits found at shallower depths at the margins of the basin. These deposits are associated with warmer conditions experienced during the Windermere Interstadial and Holocene, whilst minerogenic-rich sediments were deposited during the colder climatic conditions of the Dimlington Stadial and the Loch Lomond Stadial with rangefinder radiocarbon dates confirming this attribution. A model of lake level changes shows that drainage of the Dimlington Stadial glacial lake caused the largest fall, but there was also a further, smaller lake level fall at the end of the Windermere Interstadial and/or the start of the Loch Lomond Stadial, before the level rose in the early Holocene. The lithostratigraphic results presented here form the framework for further paleoenvironmental and paleoclimatic research at Llangorse Lake

The Confidence Database

Understanding how people rate their confidence is critical for the characterization of a wide range of perceptual, memory, motor and cognitive processes. To enable the continued exploration of these processes, we created a large database of confidence studies spanning a broad set of paradigms, participant populations and fields of study. The data from each study are structured in a common, easy-to-use format that can be easily imported and analysed using multiple software packages. Each dataset is accompanied by an explanation regarding the nature of the collected data. At the time of publication, the Confidence Database (which is available at https://osf.io/s46pr/) contained 145 datasets with data from more than 8,700 participants and almost 4 million trials. The database will remain open for new submissions indefinitely and is expected to continue to grow. Here we show the usefulness of this large collection of datasets in four different analyses that provide precise estimations of several foundational confidence-related effects

Cerebral small vessel disease genomics and its implications across the lifespan

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.Peer reviewe

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

A creeping holiday souvenir: about a misleading case of hookworm folliculitis†.

A 27-year-old Caucasian woman presented to the outpatient dermatology department of the Cliniques universitaires Saint-Luc in Brussels, Belgium, with a pruritic rash that had started a week previously while she was travelling in Thailand. She was otherwise healthy. The lesions, initially located in the sub-mammary folds and in the lumbar region, had then spread to her torso (Figure 1) despite treatment with IV dexamethasone and antihistamines. On initial examination, the eruption presented as numerous fixed erythematous follicular papules and excoriations. [...

Barriers and opportunities of digital servitization for SMEs : the effect of smart Product-Service System business models

Digital servitization enables SMEs to propose smart Product-Service Systems (PSS) integrating products and services. Limited discussion of this contemporary and challenging phenomena stimulated our in-depth literature review, which identified four key themes common to both barriers and opportunities: digital strategy, ecosystem network, internal and operational organization, and human capabilities. Industry expert focus group enabled enriching and refining these themes across smart PSS business models. Digital servitization was found to mostly benefit the SME’s digital strategy and ecosystem network and is hindered by insufficient human capabilities and underdeveloped ecosystem networks. Opportunities and barriers vary as the smart PSS business model evolves.</p

Obstacles et opportunités de la servicisation numérique des PME

International audienceAdopter une stratégie de numérisation de l'offre dite de servicisation numérique permet aux PME de se positionner non plus comme des vendeurs de produits ou de services mais comme des offreurs de solutions numériques intégrant des produits et des services intelligents afin de faire face à une concurrence accrue et apporter plus de valeur à leurs clients. Ces solutions numériques intégrées qualifiées de système produit-service (SPS) intelligent peuvent couvrir un large spectre de proposition de valeur pour le client. Elles peuvent aller d'une offre orientée produit qui associe au produit un service additionnel à une offre plus complexe orientée sur l'usage où le produit se substitue au service. En s'appuyant sur un focus group impliquant des manageurs en charge de la stratégie de numérisation au sein de 9 PME de secteurs divers, ce papier vise à identifier les obstacles et les opportunités liées à une telle stratégie pour les PME. De plus, nos résultats mettent en évidence une variabilité de ces obstacles et opportunités en fonction du type de solution SPS intelligente proposée par la PME aux clients

Obstacles et opportunités de la servicisation numérique des PME

International audienceAdopter une stratégie de numérisation de l'offre dite de servicisation numérique permet aux PME de se positionner non plus comme des vendeurs de produits ou de services mais comme des offreurs de solutions numériques intégrant des produits et des services intelligents afin de faire face à une concurrence accrue et apporter plus de valeur à leurs clients. Ces solutions numériques intégrées qualifiées de système produit-service (SPS) intelligent peuvent couvrir un large spectre de proposition de valeur pour le client. Elles peuvent aller d'une offre orientée produit qui associe au produit un service additionnel à une offre plus complexe orientée sur l'usage où le produit se substitue au service. En s'appuyant sur un focus group impliquant des manageurs en charge de la stratégie de numérisation au sein de 9 PME de secteurs divers, ce papier vise à identifier les obstacles et les opportunités liées à une telle stratégie pour les PME. De plus, nos résultats mettent en évidence une variabilité de ces obstacles et opportunités en fonction du type de solution SPS intelligente proposée par la PME aux clients

Drug reaction with eosinophilia and systemic symptoms syndrome in a patient with COVID-19.

Dear Editor, Skin rashes associated with COVID‐19 include eruptions induced by drugs prescribed for management of this infection. We report a case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient with COVID‐19. [...

Drug reaction with eosinophilia and systemic symptoms syndrome in a patient with COVID‐19

Dear Editor, Skin rashes associated with COVID‐19 include eruptions induced by drugs prescribed for management of this infection. We report a case of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a patient with COVID‐19. [...