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ABSTRACTThis paper discusses the results of a detailed analysis of the lithic assemblages from four key sites in the Lower-Scheldt basin of NW Belgium in the context of the Neolithization process beyond the agro-pastoral frontier of the European loess area. The study demonstrates both continuity and change in raw material use, lithic technology and the toolkit throughout the 5th and early 4th millennium cal BC, supporting the theory of acculturation of indigenous hunter-gatherers under the influence of southern farming groups.

Environmental changes have had an enormous impact on prehistoric hunter-gatherers as they affect the biotic landscape and availability of resources such as freshwater, edible plants, game and fish. To assess whether various innovations that took place in hunter-gatherer communities during the Boreal may be attributed to changes in the vegetation, a high-resolution pollen and macrofossil analysis of a well-AMS-dated Early Holocene peat record from the Grote Nete valley in the Belgian Campine was carried out. Shifts in the pollen assemblages indicate a change from a birch-pine woodland in the late Preboreal to pine-dominated forests in the Boreal. After the initial expansion of hazel, followed by oak and elm from the early Boreal onward, a prominent and abrupt reduction of the pollen concentration, by up to 95% over several spectra, is observed during the second half of the Boreal. This sharp decline affects all taxa and coincides with a decrease in pollen percentages of thermophilous trees and an increase of the cold-tolerant pine. This shift in pollen concentration and vegetation composition likely reflects a climatic cooling at 9.3 ka which is evident in the stable oxygen isotopic record of the Greenland ice cores. On the one hand, the vegetation dynamics are discussed in the light of the Boreal vegetation history in general and this temporary cooling more specifically. On the other hand, we discuss how these changes may have affected past hunter-gatherer communities.

ABSTRACTPathogenic E. colistrains can be classified into two major groups, based on the presence of specific virulence factors: extraintestinal pathogenic E. coli(ExPEC) and diarrheagenic E. coli(DEC). Several case reports describe that DEC can cause bloodstream infections in some rare cases. This mainly concerns a few specific sequence types that express virulence factors from both ExPEC and DEC. In this study, we retrospectively analysed 234 E. coliblood isolates with whole genome sequencing (WGS). WGS was performed on an Illumina NovaSeq6000. Genotyping was performed using BioNumerics software. The presence of genes was determined with a minimum percentage sequence identity (ID) threshold of 95% and a minimum length for sequence coverage of 95%. Three of the 234 (1.28%) isolates were defined as DEC, 182 (77.78%) as ExPEC, and 49 (20.94%) did not carry pathotype-associated virulence genes. We identified 112 different virulence genes, 48 O-antigens, and 28 H-antigens 82 STs, among the 234 analyzed isolates. ST131 and ST88 were related to healthcare-associated infections. This study provides insight into the prevalence of virulence factors in a large set of E. coliblood isolates from the UZ Brussel. It illustrates high diversity in virulence profiles and highlights the potential of DEC to carry virulence factors associated with extraintestinal infections, making it possible for unusual pathotypes to invade and survive in the bloodstream causing bacteraemia. Diarrheagenic strains causing bacteremia are rare and presently underreported, but modern sequencing techniques will better underscore their importance.

The grey wolf (Canis lupus) was the first species to give rise to a domestic population, and they remained widespread throughout the last Ice Age when many other large mammal species went extinct. Little is known, however, about the history and possible extinction of past wolf populations or when and where the wolf progenitors of the present-day dog lineage (Canis familiaris) lived1–8. Here we analysed 72 ancient wolf genomes spanning the last 100,000 years from Europe, Siberia and North America. We found that wolf populations were highly connected throughout the Late Pleistocene, with levels of differentiation an order of magnitude lower than they are today. This population connectivity allowed us to detect natural selection across the time series, including rapid fixation of mutations in the gene IFT8840,000–30,000 years ago. We show that dogs are overall more closely related to ancient wolves from eastern Eurasia than to those from western Eurasia, suggesting a domestication process in the east. However, we also found that dogs in the Near East and Africa derive up to half of their ancestry from a distinct population related to modern southwest Eurasian wolves, reflecting either an independent domestication process or admixture from local wolves. None of the analysed ancient wolf genomes is a direct match for either of these dog ancestries, meaning that the exact progenitor populations remain to be located.

A laboratory-based X-ray fluorescence (XRF) methodology is presented for standardless quantified analysis based on a monochromatic X-ray spectrometer coupled to Monte Carlo aided quantification. This procedure will be valuable for many scientific fields (e.g. archaeology, geology, etc.) where the unique nature of the investigated samples calls for the application of non-destructive techniques. To illustrate the value of the methodology, a case study is presented where flint artefacts from the Scheldt basin are analyzed in an attempt to provenance them. So far, little geochemical research has been done in this area. Our results contribute to the creation of a database that will help assign lithic artefacts to specific geological outcrops and will aid further research in this field.

ABSTRACTArchaeological lithic assemblages are often affected by burning, as evident from severe thermal damage on these artefacts. In this study, the thermal alteration of four different flint types was investigated by performing controlled heating experiments in laboratory setting. The resulting heat alterations were afterwards compared to heating of flint samples in campfire experiments, as these correspond better to the burning conditions present during prehistoric times. The microstructural and chemical changes occurring in flint during heating were analyzed using different macroscopic (visual observations and color measurements) and microscopic (optical microscopy and non-destructive X-ray micro-CT) techniques. Eventually, the terminology regarding the degree of heat exposure was refined and complemented with temperature ranges and color information for the investigated flint types. In doing so, this study provides criteria for a more objective macroscopic determination of the burning degree of archaeological flint artefacts, that could be useful in a wide range of lithic studies.

ABSTRACTDirect dates of pottery obtained from food crusts or other organic residues on the vessel surfaces can be affected by a reservoir effect and/or an old wood effect and therefore be unreliable. Hence, there is a need for alternative ways to directly date pottery. Moss is used as temper by several cultural groups of the late 6th to early 4th millennium cal BC in northwestern Europe. After the pottery is fired, charred moss remains are often preserved in the clay, so that relatively short-lived plant material with a direct chronological link to the pottery and human occupation is available for radiocarbon (14C) dating. In this study, charred moss temper is extracted for accelerator mass spectrometry (AMS) 14C dating from pottery of the Swifterbant Culture and Spiere group in the Scheldt river valley (Belgium). The moss dates are then compared to reference dates of organic macro-remains from the same sites and food crust dates with or without a reservoir effect of the same pottery. Eleven out of 13 moss dates are in line with the expected pottery age. The paired dates of moss temper and food crusts from the same potsherds confirm a freshwater reservoir effect (FRE) for the latter. We conclude that moss temper has great potential as a sample material for direct pottery dating. However, more research on the extraction and pretreatment of moss temper as well as on the reliability of moss dates is necessary in the future.

ABSTRACTThe refitting of eight Early Mesolithic artefact clusters yielded a detailed image of the flint knapping methods applied at the site of Kerkhove (BE). Apart from apparent intra-site variability, the analysis revealed a greater investment in core-shaping than is traditionally present in Early Mesolithic assemblages, combined with a clear preference for bladelet production organized from alternatingly used, opposed striking platforms. Both elements, unprecedented to some extent in Northwestern Europe, indicate continuity between Early Mesolithic technological traditions and those of the preceding, Final-Palaeolithic period.

The presence of at least two of three MRI features (necrosis, heterogeneity, and peritumoral enhancement) was an independent predictor of metastasis-free survival and overall survival.

This article focuses on pleomorphic sarcomas, which are malignant mesenchymal tumors with complex genetic background at the root of their morphologic pleomorphism. They are poorly differentiated tumors that may retain different lines of differentiation, sometimes correlating with clinicopathological or prognostic features. Accurate diagnosis in this group of tumors relies on adequate sampling due to their heterogeneity and assessment with both microscopy and large panels of immunohistochemistry. Molecular analyses have a limited role in their diagnosis as opposed to translocation-related sarcomas but may provide theranostic and important prognostic information in the future.

Morphological and morphometric bone variation between archaeological wolves and the oldest domestic dogs commonly are used to define species differences. However, reference data often have been based on small numbers, without robust statistical support. We consulted the literature on these matters in all possible languages and tested many of the proposed species differences by examining wolf and dog skeletons from several collections, accompanied by an extensive synthesis of existing literature. We thus created large reference groups, assessing data distributions and variability. We examined mandible height, width, length, and convexity; contact points of the skull on a horizontal plane; caudal shifting of the border of the hard palate; skull size; carnassials tooth size reduction; micro-anatomical differences in teeth, snout, and skull height; and snout length and width.

Les auteurs décrivent ici les présentations cliniques, les arguments diagnostics radiologiques et anatomopathologiques, le profil évolutif et le traitement des hémangioendothéliomes épithélioïdes. La grande majorité des hémangioendothéliomes épithélioïdes (90 %) présentent une translocation chromosomique réciproque t(1;3)(p36;q23–25) associée à la synthèse d’une protéine de fusion WWTR1/CAMTA1. Ces tumeurs vasculaires de bas grade peuvent être localisées ou d’emblée multifocales. Elles sont souvent lentement évolutives. Localisées, elles appellent un traitement local. Multifocales, elles nécessitent tout d’abord une surveillance attentive. Certaines d’entre elles peuvent être spontanément stables pendant des années voire des décennies. En cas de progression, il n’y a pas de standard thérapeutique. Le diagnostic doit être confirmé au sein d’un réseau spécialisé de bio pathologie (RRePS) et la prise en charge interdisciplinaire relève des centres sarcomes labellisés par l’Institut national du cancer (NetSarc).

ABSTRACTOrganic residues preserved on the outer surfaces of archaeological pottery are commonly considered to be soot and, not being subject to reservoir effects, as more reliable for radiocarbon (14C) dating compared to food crusts from the inner surface. However, unlike food crusts, outer surface residues are never analyzed prior to 14C dating. This study confronts 14C dates on inner and outer surface residues preserved on prehistoric pottery from Bazel Sluis (Belgium) with the results of stable isotope analysis and thermally assisted hydrolysis and methylation pyrolysis-gas chromatography-mass spectrometry (THM-GC-MS). These analyses clearly show that food residue is also present on the outer pottery surface, causing a possible reservoir effect on 14C dates. At Bazel, 14C dates on both the inner and outer surface residues are too old compared to dates obtained on associated animal bone. In addition, the outer surface residues systematically date younger than the inner food crusts, a discrepancy that is also known from other archaeological sites. It is suggested that these age differences are due to the mixed presence of soot and food residue on the exterior vessel wall as opposed to more homogeneous food crusts on the internal surface.

We describe a new technique for the efficient generation of high-energy ions with electromagnetic ion cyclotron waves in multi-ion plasmas. The discussed ‘three-ion’ scenarios are especially suited for strong wave absorption by a very low number of resonant ions. To observe this effect, the plasma composition has to be properly adjusted, as prescribed by theory. We demonstrate the potential of the method on the world-largest plasma magnetic confinement device, JET (Joint European Torus, Culham, UK), and the high-magnetic-field tokamak Alcator C-Mod (Cambridge, USA). The obtained results demonstrate efficient acceleration of 3He ions to high energies in dedicated hydrogen–deuterium mixtures. Simultaneously, effective plasma heating is observed, as a result of the slowing-down of the fast 3He ions. The developed technique is not only limited to laboratory plasmas, but can also be applied to explain observations of energetic ions in space-plasma environments, in particular, 3He-rich solar flares.

Mature tertiary lymphoid structures (mTLSs) are organized lymphoid structures containing B lymphocytes admixed to CD23+ follicular dendritic cells. Their presence has been linked to improved survival and sensitivity to immune checkpoint inhibitors in several cancers, emerging as a promising pancancer biomarker. However, the requirements for any biomarker are clear methodology, proven feasibility, and reliability. In 357 patients’ samples, we studied tertiary lymphoid structures (TLSs) parameters using multiplex immunofluorescence (mIF), hematoxylin-eosin-saffron (HES) staining, double CD20/CD23 staining, and single CD23 immunohistochemistry. The cohort included carcinomas (n = 211) and sarcomas (n = 146), gathering biopsies (n = 170), and surgical specimens (n = 187). mTLSs were defined as TLSs containing either a visible germinal center on HES staining or CD23+ follicular dendritic cells. Focusing on 40 TLSs assessed using mIF, double CD20/CD23 staining was less sensitive than mIF to assess maturity in 27.5% (n = 11/40) but was rescued by single CD23 staining in 90.9% (n = 10/11). In 97 patients, several samples (n = 240) were reviewed to characterize TLS distribution. The likelihood of finding TLSs in surgical material was 6.1 higher than in biopsy and 2.0 higher in primary samples than in metastasis after adjustment with a type of sample. Interrater agreement rates over 4 examiners were 0.65 (Fleiss kappa, 95% CI [0.46; 0.90]) for the presence of TLS and 0.90 for maturity (95% CI [0.83;0.99]). In this study, we propose a standardized method to screen mTLSs in cancer samples using HES staining and immunohistochemistry that can be applied to all specimens.

In proven SARS-CoV-2 infection, both the Omicron variant and vaccination were associated with lower frequency of typical COVID-19 chest CT patterns and lesser extent of disease compared with the Delta variant and nonvaccination.

Vascularized fibular autografts (VFA) are used in the oncologic skeletal reconstructions of long bones, alone or combined with massive bone allografts (MBA). Data regarding the role of imaging in assessing these complex skeletal reconstructions are lacking, and have mainly focused on Computed Tomography (CT). Our aim was to evaluate if early conventional radiography (CR) findings are correlated with the outcome of these skeletal reconstructions.

Since the first description of livestock-associated methicillin-resistant Staphylococcus aureus(LA-MRSA), a high prevalence was observed in pigs. At present, questions remain about the transmission of LA-MRSA to the general human population through pork. The objectives of the present study were to determine the prevalence of LA-MRSA in Belgian pork and to determine the role of the pork production chain and butcheries in transmission of LA-MRSA to the human population. Pig meat samples (chops, bacon, minced pork, ribs, forelimbs, and ears; n=137) originating from four butcheries (A through D) were spread plated on ChromID MRSA plates both before and after overnight enrichment culture. Suspect colonies were confirmed using a MRSA-specific triplex PCR assay and a CC398-specific PCR assay. The isolates (n=147) were further characterized by SCCmectyping, multiple-locus variable number tandem repeat analysis, and antimicrobial susceptibility testing, a selection of isolates were subjected to pulsed-field gel electrophoresis and spatyping. Direct plating revealed a MRSA prevalence of 8%. After enrichment, MRSA was isolated from 98 (72%) of 137 samples of which the majority were from rib, ear, and forelimb. The majority (97%) of obtained isolates belonged to CC398, the main LA-MRSA type. A high level of genetic diversity was noted among the isolates from one butchery. Thirty antimicrobial susceptibility profiles were found; 13 and 9% of the isolates had Cip-Tet-Tri and Gen-Kan-Tet-Tob-Tri profiles, respectively. These results indicate the importance of enrichment for MRSA detection of pork. The observed genetic diversity of the isolates indicated that the pork production chain can be considered a source of multiple MRSA types that could be transmitted to the human population through cross-contaminated meat.

At the prehistoric site of Rosalinde in Ruien (Belgium) sandstone blocks of local origin have been found in a configuration that was tentatively interpreted by the archaeologists as a hearth. These sandstones are identified as ferruginous sandstone and glauconiferous sandstone, and each block shows a discoloured rim which is not typically observed on these lithotypes. In order to confirm their use as hearth stones, the mineralogy in the discoloured rim was studied and compared to the bulk mineralogical composition by means of optical petrography, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and dithionite-citrate bicarbonate extraction (DCB). In the ferruginous sandstone, XRD and DSC illustrate the transformation of amorphous iron oxides and goethite into hematite. In the glauconiferous sandstone, however, the amount of iron oxide phases is too low for detection with XRD and DSC. In this case, the dark brown discolouration of the glauconite grains, together with the higher free iron oxide content in the rim than in the bulk as indicated by DCB analysis, are most suggestive of a mineralogical transformation due to heating. The heating temperature is estimated between 300 and 600 °C. Despite the absence of charcoal, the combined evidence obtained on the two lithotypes suggests the use of this specific stone arrangement as a hearth at the prehistoric site of Ruien.

•Combined petrography and LA-ICP-MS of Neolithic pottery from northern Belgium.•Petrographic classification of pottery was not visible in clay chemical composition.•LA-ICP-MS data alone did not allow linking sediments to pottery.•Petrography is indispensable for provenance analysis of pottery.

AbstractThe importance of radial (i.e. perpendicular to the magnetic surface) electric fields was already recognised early in the research on controlled thermonuclear fusion. An initial description of electric field effects in toroidal confinement was given by Budker. Such a configuration with combined magnetic and electric confinement (“magnetoelectric confinement”, where the electric field provides a toroidal equilibrium configuration without rotational transform) was studied by Stix, who suggested that a reactor-grade plasma under magnetoelectric confinement (electric fields of order 1 MV/cm) may reach a quasi-steady-state with ambipolar loss of electrons and some suprathermal ions (e.g. 3.5 MeV α-particles). Experiments such as on the Electric Field Bumpy Torus EFBT provided quite favourable scaling for particle confinement. The possible importance of radial electric fields for transport was in the past repeatedly established. Since the early days the plasma potential has been measured in tokamaks such as ST, TM-4 and ISX-B, but because no significant effects of the radial electric field Eron plasma transport were observed under the machine conditions at that time, no further research was conducted in tokamaks.

AbstractThe importance of radial (i.e. perpendicular to the magnetic surface) electric fields was already recognised early in the research on controlled thermonuclear fusion. An initial description of electric field effects in toroidal confinement was given by Budker. Such a configuration with combined magnetic and electric confinement (“magnetoelectric confinement”, where the electric field provides a toroidal equilibrium configuration without rotational transform) was studied by Stix, who suggested that a reactor-grade plasma under magnetoelectric confinement (electric fields of order 1 MV/cm) may reach a quasi-steady-state with ambipolar loss of electrons and some suprathermal ions (e.g. 3.5 MeV α-particles). Experiments such as on the Electric Field Bumpy Torus EFBT provided quite favourable scaling for particle confinement. The possible importance of radial electric fields for transport was in the past repeatedly established. Since the early days the plasma potential has been measured in tokamaks such as ST, TM-4 and ISXB, but because no significant effects of the radial electric field Er on plasma transport were observed under the machine conditions at that time, no further research was conducted in tokamaks.

Background: Elevated oxidized low‐density lipoprotein (oxLDL) is associated with atherosclerosis and high cardiovascular risk. Previously, we identified 18 genes in coronary plaque macrophages of hypercholesterolemic pigs that correlated with plaque oxLDL. Objective: To determine which of these genes were differentially expressed in blood monocytes and correlated with blood and plaque oxLDL and with plaque complexity. Methods: RNA expression in monocytes of 27 hypercholesterolemic and 12 control pigs was analyzed with quantitative real‐time polymerase chain reaction. Results: Five of 12 genes with detectable expression in monocytes were overexpressed (at P<0.01 level) in blood monocytes of hypercholesterolemic pigs: ABCA1, SCD, IRF1, SDC2, and TLR2. ABCA1RNA expression in blood monocytes correlated with blood oxLDL, and its RNA and protein expression was increased prior to atherosclerotic plaque formation. Higher expression of ABCA1in monocytes was associated with higher plaque complexity and higher plaque oxLDL. Immunostaining of coronary plaques showed the association of ABCA1 with macrophages, lipids, and oxLDL; ABCA1 protein correlated with plaque oxLDL (R2 = 0.66; P<0.0001). In THP‐1 monocytes, oxLDL induced ABCA1expression. OxLDL‐induced foam cell generation in THP‐1 and human monocyte‐derived macrophages was associated with a further increase of ABCA1expression. Conclusions: The increase of ABCA1 in monocytes in association with blood oxLDL prior to atherosclerotic lesion formation and the association of higher ABCA1 with higher plaque complexity suggests that ABCA1 is an early biomarker of atherosclerosis. Studies in humans are warranted.

•Burnt lithic artefacts are abundant in Mesolithic assemblages.•An experimental approach to study the impact of burning on flint is presented.•Physical changes of flint are linked to burning temperature and position in fire.•Campfire experiments contribute to the understanding of prehistoric fire management.•Experimentation aids in reconstructing the relation between hearths and domestic activities.

Hess: Roche: Honoraria; Roche, CTI, Pfizer, Celgene: Research Funding; Janssen: Honoraria; Novartis: Honoraria; Celgene: Honoraria; Pfizer: Honoraria. LaRosee:Pfizer: Honoraria. Keller:Spectrum Pharmaceutical: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria. Witzens-Harig:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dreyling:Roche: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Witzens-Harig: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Viardot:Pfizer: Honoraria; Takeda: Other: travel support; Roche: Honoraria; BMS: Consultancy; Janssen: Consultancy; Amgen: Consultancy. Keller:Roche: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Spectrum Pharmaceutical: Consultancy, Membership on an entity's Board of Directors or advisory committees. Buske:Celltrion, Inc.: Consultancy, Honoraria. Meissner:Amgen: Other: Travel Support; Takeda: Other: Travel Support; Teva: Other: Travel Support; Celgene: Other: Travel Support. LaRosee:Pfizer: Honoraria. Marks:Pfizer: Honoraria. Hess:Celgene: Honoraria; Roche, CTI, Pfizer, Celgene: Research Funding; Janssen: Honoraria; Roche: Honoraria; Pfizer: Honoraria; Novartis: Honoraria.

Purpose.

Background: mTOR inhibition has been shown to be effective in various subtypes of malignant lymphomas (Smith et al, JCO 2010). Furthermore, in relapsed MCL a phase III trial demonstrated superiority of Temsirolimus to chemotherapy. Although novel treatment options as Ibrutinib have changed the treatment landscape for MCL, no curative potential could be shown for this approach and novel concepts continue to be needed. Several trials provided promising results when Temsirolimus is combined with agents like Rituximab (Ansell et al, Lancet Oncology 2011) or chemoimmunotherapy, as shown in part I (phase I) of the reported trial (Hess, Leukemia, 2015). We now report the final analysis of phase I and II results.

Witzens-Harig: Pfizer: Honoraria, Research Funding; Roche: Honoraria. Keller:Roche: Consultancy, Honoraria; Pfizer: Consultancy. Viardot:Roche: Honoraria; CTI: Consultancy; Pfizer: Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy. Buske:Roche: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Gilead: Honoraria. Ho:Sanofi: Research Funding. Hess:Janssen, Roche, Celgene, Novartis: Consultancy; Pfizer, Janssen, Roche, Mundipharma: Honoraria, Research Funding.

Purpose.