Location of the Deposit of Papyri from the Temple Library at Tebtunis Identified

In 1931 at Tebtunis in the Fayyum oasis, Carlo Anti and Gilbert Bagnani discovered one of the largest deposit of Egyptian literary papyri ever made and moreover it originally derived from the library of the temple itself. The precise location of this deposit, however, has never been clear, because there was not the possibility to see and study the whole archive, collected by Anti, made by photographic materials and written documents. On the contrary, now Carlo Anti\u2019s archive has recently been reordered at the Istituto Veneto and in the Museum of Archaeological Sciences and Arts (University of Padua)

CRACM/Orai ion channel expression and function in human lung mast cells

BackgroundInflux of extracellular Ca2+ into human lung mast cells (HLMCs) is essential for the FcεRI-dependent release of preformed granule-derived mediators and newly synthesized autacoids and cytokines. However, the identity of the ion channels underlying this Ca2+ influx is unknown. The recently discovered members of the CRACM/Orai ion channel family that carries the Ca2+ release–activated Ca2+ current are candidates.ObjectivesTo investigate the expression and function of CRACM channels in HLMCs.MethodsCRACM mRNA, protein, and functional expression were examined in purified HLMCs and isolated human bronchus.ResultsCRACM1, -2, and -3 mRNA transcripts and CRACM1 and -2 proteins were detectable in HLMCs. A CRACM-like current was detected following FcεRI-dependent HLMC activation and also in HLMCs dialyzed with 30 μM inositol triphosphate. The Ca2+-selective current obtained under both conditions was blocked by 10 μM La3+ and Gd3+, known blockers of CRACM channels, and 2 distinct and specific CRACM-channel blockers—GSK-7975A and Synta-66. Both blockers reduced FcεRI-dependent Ca2+ influx, and 3 μM GSK-7975A and Synta-66 reduced the release of histamine, leukotriene C4, and cytokines (IL-5/-8/-13 and TNFα) by up to 50%. Synta-66 also inhibited allergen-dependent bronchial smooth muscle contraction in ex vivo tissue.ConclusionsThe presence of CRACM channels, a CRACM-like current, and functional inhibition of HLMC Ca2+ influx, mediator release, and allergen-induced bronchial smooth muscle contraction by CRACM-channel blockers supports a role for CRACM channels in FcεRI-dependent HLMC secretion. CRACM channels are therefore a potential therapeutic target in the treatment of asthma and related allergic diseases

The Leukos Survey Project

From 2008 to 2011, we conducted archaeological explorations in the area known today as Kato Leukos on the Greek island of Karpathos. Our interest in the site was sparked by the late Gilbert Bagnani. In June of 1923, as a graduate student and a member of the Italian School of Archaeology at Athens, Bagnani traveled to Karpathos in the company of the director of the School and a fellow student. While investigating the visible remains at Kato Leukos, Bagnani commented in his notebook, “there can be no doubt that it is the site of an ancient city, perhaps Nysiros, the only one of the four cities of Karpathos whose site is still unknown.” His suggestion was in direct response to Strabo’s claim that Karpathos was home to a tetrapolis. Three of the four cities, Pigadia, Arkassa and Vrykous, are known, the fourth remains unidentified (fig. 1). In addition, Bagnani also noted architectural blocks with cuttings and moldings characteristic of temple architecture strewn about the upper portion of the site. He did not publish his work, but deposited his field notes in the archives at Trent University and the Italian School at Athens. Armed with Bagnani’s observations, we superficially inspected the area in 2004 and then commenced four seasons of intensive archaeological surface survey in 2008. Our goals in the field were fourfold, to determine: 1) the chronological parameters of the settlement; 2) the extent of the settlement and its relationship to the land- and sea-scape; 3) the settlement’s urban institutions, and; 4) the settlement’s role in seafaring and maritime trade. Although the results of our field work could not confirm Bagnani’s suggestion that Kato Leukos was the fourth member of Strabo’s tetrapolis, our survey established the remains of two later settlements: a 4th- to 6th-century CE port settlement (hereafter, Leukos) and an 11th- to 13th-century CE fortified islet (hereafter, Sokastro) (fig. 2). Karpathos lay at the crossroads of two major shipping lanes and the ceramic evidence recorded at both settlements confirms their participation in seaborne trade.5 Because Karpathos lacks natural resources and arable land, the Leukos Survey Project sought to determine whether the two settlements were entirely dependent for survival on the ships transporting their tradable cargos which plied the island’s waters and sheltered in its natural harbors. The tumultuous history of the Aegean during the medieval period no doubt also contributed to the short-lived nature of both settlements. Our project was the first scientifically-based archaeological survey conducted on Karpathos, and the preliminary results presented here begin to define the medieval history of the island with newly-gathered data.University College Dubli

Multicentre, prospective, randomised, open-label, blinded end point trial of the efficacy of allopurinol therapy in improving cardiovascular outcomes in patients with ischaemic heart disease: protocol of the ALL-HEART study

Introduction Ischaemic heart disease (IHD) is one of the most common causes of death in the UK and treatment of patients with IHD costs the National Health System (NHS) billions of pounds each year. Allopurinol is a xanthine oxidase inhibitor used to prevent gout that also has several positive effects on the cardiovascular system. The ALL-HEART study aims to determine whether allopurinol improves cardiovascular outcomes in patients with IHD. Methods and Analysis The ALL-HEART study is a multicentre, controlled, prospective, randomised, open-label blinded end point (PROBE) trial of allopurinol (up to 600 mg daily) versus no treatment in a 1:1 ratio, added to usual care, in 5215 patients aged 60 years and over with IHD. Patients are followed up by electronic record linkage and annual questionnaires for an average of 4 years. The primary outcome is the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes include all-cause mortality, quality of life and cost-effectiveness of allopurinol. The study will end when 631 adjudicated primary outcomes have occurred. The study is powered at 80% to detect a 20% reduction in the primary end point for the intervention. Patient recruitment to the ALL-HEART study started in February 2014. Ethics and Dissemination The study received ethical approval from the East of Scotland Research Ethics Service (EoSRES) REC 2 (13/ES/0104). The study is event-driven and results are expected after 2019. Results will be reported in peer-reviewed journals and at scientific meetings. Results will also be disseminated to guideline committees, NHS organisations and patient groups

Holocene drainage systems of the English Fenland : roddons and their environmental significance

The roddons of the English Fenlands are fossilised silt and sand-filled tidal creek systems of mid- to late-Holocene age, incised into contemporaneous clay deposits. However, anthropogenic change (drainage and agriculture) has caused the former channels to become positive topographical features. Three stratigraphically discrete generations of roddon have been discriminated. They all show well-developed dendritic meander patterns, but there is little or no evidence of sand/silt infill during meandering; thus, unlike modern tidal creeks and rivers they typically lack laterally stacked point bar deposits, suggesting rapid infill. Major “trunk” roddons are rich in fine sands and there is little change in grain size from roddon mouth to the upper reaches, suggesting highly effective sand transport mechanisms and uniform conditions of deposition. Tributaries are silt-rich, while minor tributaries also have a significant clay component. During infill, active drainage networks appear to have been choked by sediment, converting mudflat/salt-marsh environments into widespread peat-forming freshwater reed swamps

Dietary garlic and hip osteoarthritis: evidence of a protective effect and putative mechanism of action

Background Patterns of food intake and prevalent osteoarthritis of the hand, hip, and knee were studied using the twin design to limit the effect of confounding factors. Compounds found in associated food groups were further studied in vitro. Methods Cross-sectional study conducted in a large population-based volunteer cohort of twins. Food intake was evaluated using the Food Frequency Questionnaire; OA was determined using plain radiographs. Analyses were adjusted for age, BMI and physical activity. Subsequent in vitro studies examined the effects of allium-derived compounds on the expression of matrix-degrading proteases in SW1353 chondrosarcoma cells. Results Data were available, depending on phenotype, for 654-1082 of 1086 female twins (median age 58.9 years; range 46-77). Trends in dietary analysis revealed a specific pattern of dietary intake, that high in fruit and vegetables, showed an inverse association with hip OA (p = 0.022). Consumption of 'non-citrus fruit' (p = 0.015) and 'alliums' (p = 0.029) had the strongest protective effect. Alliums contain diallyl disulphide which was shown to abrogate cytokine-induced matrix metalloproteinase expression. Conclusions Studies of diet are notorious for their confounding by lifestyle effects. While taking account of BMI, the data show an independent effect of a diet high in fruit and vegetables, suggesting it to be protective against radiographic hip OA. Furthermore, diallyl disulphide, a compound found in garlic and other alliums, represses the expression of matrix-degrading proteases in chondrocyte-like cells, providing a potential mechanism of action

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease:the ALL-HEART RCT and economic evaluation

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol. Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease. Design: Prospective, randomised, open-label, blinded endpoint multicentre clinical trial. Setting: Four hundred and twenty-four UK primary care practices. Participants: Aged 60 years and over with ischaemic heart disease but no gout. Interventions: Participants were randomised (1: 1) using a central web-based randomisation system to receive allopurinol up to 600 mg daily that was added to usual care or to continue usual care. Main outcome measures: The primary outcome was the composite of non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Secondary outcomes were non-fatal myocardial infarction, non-fatal stroke, cardiovascular death, all-cause mortality, hospitalisation for heart failure, hospitalisation for acute coronary syndrome, coronary revascularisation, hospitalisation for acute coronary syndrome or coronary revascularisation, all cardiovascular hospitalisations, quality of life and cost-effectiveness. The hazard ratio (allopurinol vs. usual care) in a Cox proportional hazards model was assessed for superiority in a modified intention-to-treat analysis. Results: From 7 February 2014 to 2 October 2017, 5937 participants were enrolled and randomised to the allopurinol arm (n = 2979) or the usual care arm (n = 2958). A total of 5721 randomised participants (2853 allopurinol; 2868 usual care) were included in the modified intention-to-treat analysis population (mean age 72.0 years; 75.5% male). There was no difference between the allopurinol and usual care arms in the primary endpoint, 314 (11.0%) participants in the allopurinol arm (2.47 events per 100 patient-years) and 325 (11.3%) in the usual care arm (2.37 events per 100 patient-years), hazard ratio 1.04 (95% confidence interval 0.89 to 1.21); p = 0.65. Two hundred and eighty-eight (10.1%) participants in the allopurinol arm and 303 (10.6%) participants in the usual care arm died, hazard ratio 1.02 (95% confidence interval 0.87 to 1.20); p = 0.77. The pre-specified health economic analysis plan was to perform a ‘within trial’ cost-utility analysis if there was no statistically significant difference in the primary endpoint, so NHS costs and quality-adjusted life-years were estimated over a 5-year period. The difference in costs between treatment arms was +£115 higher for allopurinol (95% confidence interval £17 to £210) with no difference in quality-adjusted life-years (95% confidence interval −0.061 to +0.060). We conclude that there is no evidence that allopurinol used in line with the study protocol is cost-effective. Limitations: The results may not be generalisable to younger populations, other ethnic groups or patients with more acute ischaemic heart disease. One thousand six hundred and thirty-seven participants (57.4%) in the allopurinol arm withdrew from randomised treatment, but an on-treatment analysis gave similar results to the main analysis. Conclusions: The ALL-HEART study showed that treatment with allopurinol 600 mg daily did not improve cardiovascular outcomes compared to usual care in patients with ischaemic heart disease. We conclude that allopurinol should not be recommended for the secondary prevention of cardiovascular events in patients with ischaemic heart disease but no gout.</p

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease : the ALL-HEART RCT and economic evaluation

Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 11/36/41) and is published in full in Health Technology Assessment; Vol. 28, No. 18. See the NIHR Funding and Awards website for further award information.Peer reviewe