The Macquenoise sandstone : a suitable Lochkovian raw material for ancient millstones : quarries, properties, manufacture and distribution (Belgium-France)

International audienceSince a few years a French-Belgian team of archeologists and geologists work on the characterization of ancient quern stones and millstones (mainly from the Antique period) linked with the identification of their stratigraphical and geographical provenances.This fruitful collaboration aims at reconstructing the ancient commercial roads and economic organization of territories during that period.In addition to the better-known volcanic rocks from the Eifel area, our study revealed the frequent occurrence of particular Devonian conglomerates and sandstones from the Ardenne area, as raw materials for the manufacturing of querns and millstones. The latter sandstones as well as the related antique millstone quarries, form an important and until now undervalued geological and cultural heritage in Belgium.Near the Ardenne border between France and Belgium, the earliest Devonian (Lochkovian) sediments deposited on the Caledonian substrate are conglomerates, which are interpreted as continental alluvial fans. The first marine sediments are littoral sandstones/quartzites or shales/slates. A sandstone formation, formally defined as the “Arkose d’Haybes” is closely linked to the former Lochkovian conglomerates (called also the “Poudingue de Fépin”). The outcrops of this particular formation around the reference localities of Haybes, Fépin and Hargnies (Ardennes, France), show a partly recrystallized, well-sorted grey to greenish sandstone (turbidite facies) with wine-red coloured joints. Another important area displaying old quarries in the same formation is located between Hirson (Aisne, France) and Macquenoise (Hainaut, Belgium): here, a more homogenous grey coarse sandstone facies occurs, with a better consistency and small amounts of dark green tourmaline crystals.These detrital formations were locally quarried, not only for building stones but also for the production of querns and millstones. The huge Proto-historical and Roman millstone quarries in Lochkovian conglomerates and sandstones from Macquenoise are known since the 19th century. Even if the lack of recent archeological excavations do not allow yet to precise the exact age of their quarrying, the dating of the various products derived from these quarries allow to consider the duration of the active extraction and how far the millstones from Macquenoise area were transported into the northern Gallo-Roman provinces

Deactivation of endothelium and reduction in angiogenesis in psoriatic skin and synovium by low dose infliximab therapy in combination with stable methotrexate therapy: a prospective single-centre study

Psoriasis and psoriatic arthritis are inflammatory diseases that respond well to anti-tumour necrosis factor-α therapy. To evaluate the effects of anti-tumour necrosis factor-α treatment on expression of adhesion molecules and angiogenesis in psoriatic lesional skin and synovial tissue, we performed a prospective single-centre study with infliximab therapy combined with stable methotrexate therapy. Eleven patients with both active psoriasis and psoriatic arthritis received infusions of infliximab (3 mg/kg) at baseline, and at weeks 2, 6, 14 and 22 in an open-label study. In addition, patients continued to receive stable methotrexate therapy in dosages ranging from 5 to 20 mg/week. Clinical assessments, including Psoriasis Area and Severity Index (PASI) and Disease Activity Score (DAS), were performed at baseline and every 2 weeks afterward. In addition, skin biopsies from a target psoriatic plaque and synovial tissue biopsies from a target joint were taken before treatment and at week 4. Immunohistochemical analysis was performed to detect the number of blood vessels, the expression of adhesion molecules and the presence of vascular growth factors. Stained sections were evaluated by digital image analysis. At week 16, the mean PASI was reduced from 12.3 ± 2.4 at baseline to 1.8 ± 0.4 (P ≤ 0.02). The mean DAS was reduced from 6.0 ± 0.5 to 3.6 ± 0.6 (P ≤ 0.02). We found some fluctuations in DAS response as compared with the change in PASI, with the latter exhibiting a steady decrease over time. After 4 weeks the cell infiltrate was reduced in both skin and synovium. There was a significant reduction in the number of blood vessels in dermis and synovium at week 4. A significant reduction in the expression of α(v)β(3 )integrin, a marker of neovascularization, was also found in both skin and synovium at week 4. In addition, a significant reduction in the expression of adhesion molecules was observed in both skin and synovium at week 4. We also observed a trend toward reduced expression of vascular endothelial growth factor in both skin and synovium. In conclusion, low-dose infliximab treatment leads to decreased neoangiogenesis and deactivation of the endothelium, resulting in decreased cell infiltration and clinical improvement in psoriasis and psoriatic arthritis

The macquenoise sandstone (Devonian – Lochkovian), a suitable raw material for ancient querns and millstones : quarries, properties, manufacture and distribution in France and Belgium

For some years, a French-Belgian team of archaeologists and geologists is investigating the provenance of ancient quern-stones and millstones. Their study revealed the frequent occurrence of particular coarse sandstones derived from Lower Devonian strata in the Ardenne region, known as either the “Arkose of Haybes” by geologists or the “Arkose of Macquenoise” by archaeologists. Material for Late Iron Age and Roman quern-stones and millstones was quarried from open pits located west of the border between France and Belgium, between the Belgian village of Macquenoise (Commune of Momignies, Province of Hainaut) and the French town of Hirson (Aisne Department, Hauts-de-France region). This paper describes the raw materials, presents the different types of grindstones produced through historical times and provides a detailed diffusion map of the millstones

Querns and mills during Roman times at the northern frontier of the Roman Empire (Belgium, Northern France, Southern Netherlands, Western Germany): Unraveling geological and geographical provenances, a multidisciplinary research project

This paper presents the results of a multi-disciplinary provenance study of querns and millstones during the Roman period (1st-4th century CE) in the northern part of the Roman Empire (provinces of Gallia Belgica and Germania Inferior). Comparative petrographical, mineralogical and geochemical analysis allowed an international team of archaeologists and geologists to identify the different raw materials used for the manufacturing of querns and millstones. As a result, (litho-) stratigraphic assignments as well as geological-geographical provenances are suggested or corroborated for the broad spectrum of these natural geo-materials. We give evidence for the exploitation of at least seven different rock types. They include sedimentary rocks (fine- to coarse-grained quartzitic and arkosic sandstones, conglomerates, limestones) and volcanic rocks (vesicular lavas) derived from different geological strata in the following geological-geographical settings: the volcanic Eifel area (Pleistocene lava), the Ardennes Massif (Palaeozoic sedimentary rocks) and the Paris and Northern Sea Basin (Cenozoic sedimentary rocks). Furthermore we show that a large diversity existed within different productions (different types of hand-mills and mechanical powered mills) and distribution patterns. This paper provides new data which will lead to new insights into the socio-economics of the local “Gallo-Roman” communities and into their networks within the northern Roman Empire

Functional health status in subjects after a motor vehicle accident, with emphasis on whiplash associated disorders: design of a descriptive, prospective inception cohort study

Contains fulltext : 70254.pdf (publisher's version ) (Open Access)BACKGROUND: The clinical consequences of whiplash injuries resulting from a motor vehicle accident (MVA) are poorly understood. Thereby, there is general lack of research on the development of disability in patients with acute and chronic Whiplash Associated Disorders. METHODS/DESIGN: The objective is to describe the design of an inception cohort study with a 1-year follow-up to determine risk factors for the development of symptoms after a low-impact motor vehicle accident, the prognosis of chronic disability, and costs. Victims of a low-impact motor vehicle accident will be eligible for participation. Participants with a Neck Disability Index (NDI) score of 7 or more will be classified as experiencing post-traumatic neck pain and will enter the experimental group. Participants without complaints (a NDI score less than 7) will enter the reference group. The cohort will be followed up by means of postal questionnaires and physical examinations at baseline, 3 months, 6 months, and 12 months. Recovery from whiplash-associated disorders will be measured in terms of perceived functional health, and employment status (return to work). Life tables will be generated to determine the 1-year prognosis of whiplash-associated disorders, and risk factors and prognostic factors will be assessed using multiple logistic regression analysis. DISCUSSION: Little is known about the development of symptoms and chronic disability after a whiplash injury. In the clinical setting, it is important to identify those people who are at risk of developing chronic symptoms.This inception prospective cohort study will provide insight in the influence of risk factors, of the development of functional health problems, and costs in people with whiplash-associated disorders

Epigenome-wide association study of incident type 2 diabetes:a meta-analysis of five prospective European cohorts

AIMS/HYPOTHESIS: Type 2 diabetes is a complex metabolic disease with increasing prevalence worldwide. Improving the prediction of incident type 2 diabetes using epigenetic markers could help tailor prevention efforts to those at the highest risk. The aim of this study was to identify predictive methylation markers for incident type 2 diabetes by combining epigenome-wide association study (EWAS) results from five prospective European cohorts.METHODS: We conducted a meta-analysis of EWASs in blood collected 7-10 years prior to type 2 diabetes diagnosis. DNA methylation was measured with Illumina Infinium Methylation arrays. A total of 1250 cases and 1950 controls from five longitudinal cohorts were included: Doetinchem, ESTHER, KORA1, KORA2 and EPIC-Norfolk. Associations between DNA methylation and incident type 2 diabetes were examined using robust linear regression with adjustment for potential confounders. Inverse-variance fixed-effects meta-analysis of cohort-level individual CpG EWAS estimates was performed using METAL. The methylGSA R package was used for gene set enrichment analysis. Confirmation of genome-wide significant CpG sites was performed in a cohort of Indian Asians (LOLIPOP, UK).RESULTS: The meta-analysis identified 76 CpG sites that were differentially methylated in individuals with incident type 2 diabetes compared with control individuals (p values &lt;1.1 × 10-7). Sixty-four out of 76 (84.2%) CpG sites were confirmed by directionally consistent effects and p values &lt;0.05 in an independent cohort of Indian Asians. However, on adjustment for baseline BMI only four CpG sites remained genome-wide significant, and addition of the 76 CpG methylation risk score to a prediction model including established predictors of type 2 diabetes (age, sex, BMI and HbA1c) showed no improvement (AUC 0.757 vs 0.753). Gene set enrichment analysis of the full epigenome-wide results clearly showed enrichment of processes linked to insulin signalling, lipid homeostasis and inflammation.CONCLUSIONS/INTERPRETATION: By combining results from five European cohorts, and thus significantly increasing study sample size, we identified 76 CpG sites associated with incident type 2 diabetes. Replication of 64 CpGs in an independent cohort of Indian Asians suggests that the association between DNA methylation levels and incident type 2 diabetes is robust and independent of ethnicity. Our data also indicate that BMI partly explains the association between DNA methylation and incident type 2 diabetes. Further studies are required to elucidate the underlying biological mechanisms and to determine potential causal roles of the differentially methylated CpG sites in type 2 diabetes development.</p

Daily functioning and self-management in patients with chronic low back pain after an intensive cognitive behavioral programme for pain management

Chronic low back pain (CLBP) is associated with persistent or recurrent disability which results in high costs for society. Cognitive behavioral treatments produce clinically relevant benefits for patients with CLBP. Nevertheless, no clear evidence for the most appropriate intervention is yet available. The purpose of this study is to evaluate the mid-term effects of treatment in a cohort of patients with CLBP participating in an intensive pain management programme. The programme provided by RealHealth-Netherlands is based on cognitive behavioral principles and executed in collaboration with orthopedic surgeons. Main outcome parameters were daily functioning (Roland and Morris Disability Questionnaire and Oswestry Disability Questionnaire), self-efficacy (Pain Self-Efficacy Questionnaire) and quality of life (Short Form 36 Physical Component Score). All parameters were measured at baseline, last day of residential programme and at 1 and 12 months follow-up. Repeated measures analysis was applied to examine changes over time. Clinical relevance was examined using minimal clinical important differences (MCID) estimates for main outcomes. To compare results with literature effect sizes (Cohen’s d) and Standardized Morbidity Ratios (SMR) were determined. 107 patients with CLBP participated in this programme. Mean scores on outcome measures showed a similar pattern: improvement after residential programme and maintenance of results over time. Effect sizes were 0.9 for functioning, 0.8 for self-efficacy and 1.3 for physical functioning related quality of life. Clinical relevancy: 79% reached MCID on functioning, 53% on self-efficacy and 80% on quality of life. Study results on functioning were found to be 36% better and 2% worse when related to previous research on, respectively, rehabilitation programmes and spinal surgery for similar conditions (SMR 136 and 98%, respectively). The participants of this evidence-based programme learned to manage CLBP, improved in daily functioning and quality of life. The study results are meaningful and comparable with results of spinal surgery and even better than results from less intensive rehabilitation programmes

Staying at work with back pain: patients' experiences of work-related help received from GPs and other clinicians. A qualitative study

<p>Abstract</p> <p>Background</p> <p>Low back pain commonly affects work ability, but little is known about the work-related help and advice that patients receive from GPs and other clinicians. The purpose of this study was to explore the experiences of employed people with back pain and their perceptions of how GPs and other clinicians have addressed their work difficulties.</p> <p>Methods</p> <p>A qualitative approach with thematic analysis was used. Individual interviews were carried out with twenty-five employed patients who had been referred for back pain rehabilitation. All had expressed concern about their ability to work due to low back pain.</p> <p>Results</p> <p>The perception of the participants was that GPs and other clinicians had provided little or no work-focused guidance and support and rarely communicated with employers. Sickness certification was the main method that GPs used to manage participants' work problems. Few had received assistance with temporary modifications and many participants had remained in work despite the advice they had received. There was little expectation of what GPs and other clinicians could offer to address work issues.</p> <p>Conclusions</p> <p>These findings question the ability of GPs and other clinicians to provide work-focused support and advice to patients with low back pain. Future research is recommended to explore how the workplace problems of patients can be best addressed by health professionals.</p

N6-Methyladenosine Promotes TNF mRNA Degradation In CD4+ T Lymphocytes

N6-methyladenosine (m6A) is a RNA modification that can regulate post-transcriptional processes including RNA stability, translation, splicing, and nuclear export. In CD4+ lymphocytes, m6A modifications have been demonstrated to play a role in early differentiation processes. The role of m6A in CD4+ T cell activation and effector function remains incompletely understood. To assess the role of m6A in CD4+ T lymphocyte activation and function, we assessed the transcriptome-wide m6A landscape of human primary CD4+ T cells by methylated RNA immunoprecipitation sequencing. Stimulation of the T cells impacted the m6A pattern of hundreds of transcripts including tumor necrosis factor (TNF). m6A methylation was increased on TNF messenger RNA (mRNA) after activation, predominantly in the 3' untranslated region of the transcript. Manipulation of m6A levels in primary human T cells, the directly affected the expression of TNF. Furthermore, we identified that the m6A reader protein YTHDF2 binds m6A-methylated TNF mRNA, and promotes its degradation. Taken together, this study demonstrates that TNF expression in CD4+ T lymphocytes is regulated via m6A and YTHDF2, thereby providing novel insight into the regulation of T cell effector functions

Increasing capacity for the treatment of common musculoskeletal problems: A non-inferiority RCT and economic analysis of corticosteroid injection for shoulder pain comparing a physiotherapist and orthopaedic surgeon

Background Role substitution is a strategy employed to assist health services manage the growing demand for musculoskeletal care. Corticosteroid injection is a common treatment in this population but the efficacy of its prescription and delivery by physiotherapists has not been established against orthopaedic standards. This paper investigates whether corticosteroid injection given by a physiotherapist for shoulder pain is as clinically and cost effective as that from an orthopaedic surgeon. Methods A double blind non-inferiority randomized controlled trial was conducted in an Australian public hospital orthopaedic outpatient service, from January 2013 to June 2014. Adults with a General Practitioner referral to Orthopaedics for shoulder pain received subacromial corticosteroid and local anaesthetic injection prescribed and delivered independently by a physiotherapist or a consultant orthopaedic surgeon. The main outcome measure was total Shoulder Pain and Disability Index (SPADI) score at baseline, six and 12 weeks, applying a non-inferiority margin of 15 points. Secondary outcomes tested for superiority included pain, shoulder movement, perceived improvement, adverse events, satisfaction, quality of life and costs. Results 278 participants were independently assessed by the physiotherapist and the orthopaedic surgeon, with 64 randomised (physiotherapist 33, orthopaedic surgeon 31). There were no significant differences in baseline characteristics between groups. Non-inferiority of injection by the physiotherapist was declared from total SPADI scores at 6 and 12 weeks (upper limit of the 95% one-sided confidence interval 13.34 and 7.17 at 6 and 12 weeks, respectively). There were no statistically significant differences between groups on any outcome measures at 6 or 12 weeks. From the perspective of the health funder, the physiotherapist was less expensive. Conclusions Corticosteroid injection for shoulder pain, provided by a suitably qualified physiotherapist is at least as clinically effective, and less expensive, compared with similar care delivered by an orthopaedic surgeon. Policy makers and service providers should consider implementing this model of care