123 research outputs found

    The introduction of Corded Ware Culture at a local levely:An exploratory study of cultural change during the Late Neolithic of the Dutch West Coast through ceramic technology

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    The introduction of the Corded Ware Culture (3000–2500 BCE) is considered a formative event in Europe's past. Ancient DNA analyses demonstrate that migrations played a crucial role in this event. However, these analyses approach the issue at a supra-regional scale, leaving questions about the regional and local impact of this event unresolved. This study pilots an approach to ceramics that brings this small-scale impact into focus by using the transmission of ceramic technology as a proxy for social change. It draws on ethno-archaeological studies of the effects of social changes on the transmission of ceramic production techniques to hypothesise the impact of three idealised scenarios that archaeologists have proposed for the introduction of Corded Ware Culture: migration, diffusion, and network interactions. Subsequently, it verifies these hypotheses by integrating geochemical (WDXRF), mineralogical (petrography), and macromorphological analysis of ceramics with network analysis. This method is applied to 30 Late Neolithic ceramic vessels from three sites in the western coastal area of the Netherlands (Hazerswoude-Rijndijk N11, Zandwerven, and Voorschoten-De Donk). This study concludes that the introduction of Corded Ware material culture is a process that varies from site to site in the western coastal area of the Netherlands. Moreover, the introduction of the Corded Ware Culture is characterised by continuity in technological traditions throughout the study area, indicating a degree of social continuity despite typological changes in ceramic

    Protein energy malnutrition predicts complications in liver cirrhosis

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    Cellular mechanisms in basic and clinical gastroenterology and hepatolog

    Enhancement of feline immunodeficiency virus infection after immunization with envelope glycoprotein subunit vaccines.

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    Cats were immunized three times with different recombinant feline immunodeficiency virus (FIV) candidate vaccines. Recombinant vaccinia virus (rVV)-expressed envelope glycoprotein with (vGR657) or without (vGR657 x 15) the cleavage site and an FIV envelope bacterial fusion protein (beta-Galactosidase-Env) were incorporated into immune-stimulating complexes or adjuvanted with Quil A. Although all immunized cats developed antibodies against the envelope protein, only the cats vaccinated with the rVV-expressed envelope glycoproteins developed antibodies which neutralized FIV infection of Crandell feline kidney cells. These antibodies failed to neutralize infection of thymocytes with a molecularly cloned homologous FIV. After the third immunization the cats were challenged with homologous FIV. Two weeks after challenge the cell-associated viral load proved to be significantly higher in the cats immunized with vGR657 and vGR657 x 15 than in the other cats. The cats immunized with vGR657 and vGR657 x 15 also developed antibodies against the Gag proteins more rapidly than the cats immunized with beta-Galactosidase-Env or the control cats. This suggested that immunization with rVV-expressed glycoprotein of FIV results in enhanced infectivity of FIV. It was shown that the observed enhancement could be transferred to naive cats with plasma collected at the day of challenge

    Bacterial infections in cirrhosis: Role of proton pump inhibitors and intestinal permeability

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    Background Cirrhotic patients are at considerable risk for bacterial infections, possibly through increased intestinal permeability and bacterial overgrowth. Proton pump inhibitors (PPIs) may increase infection risk. We aimed to explore the potential association between PPI use and bacterial infection risk in cirrhotic patients and potential underlying mechanisms in complementary patient and animal models. Materials and methods Bacterial overgrowth was determined in jejunum of 30 rats randomly allocated to 6-week PPI treatment, gastrectomy or no treatment. In 84 consecutive cirrhotic patients, bacterial infection risk was prospectively assessed and related to PPI use. Intestinal permeability was determined by polyethylene glycol (PEG) test in nine healthy individuals and 12 cirrhotic patients. Results Bacterial overgrowth was much more common in jejunum of rats treated with PPI or gastrectomy compared with nontreated rats. Twenty-four patients (29%) developed a bacterial infection during a median follow-up of 28months. Although PPI users tended to experience infection more often than patients without PPI therapy, PPI use was not an independent predictor of bacterial infection (HR 1·2, 95% CI 0·5-3·0, P=0·72), after correction for Child-Pugh class (HR 3·6, 95% CI 1·5-8·7, P=0·004) and age (HR 1·05, 95%CI 1·01-1·09, P=0·02). In cirrhotic patients, 24-h urinary recovery of PEGs 1500 and 3350 was significantly higher compared with healthy controls. Conclusions Although in our animal model PPIs induced intestinal overgrowth, stage of liver disease rather than PPI use was the predominant factor determining infection risk in cirrhotic patients. Increased intestinal permeability may be a factor contributing to infection risk

    Evaluation of thromboelastometry, thrombin generation and plasma clot lysis time in patients with bleeding of unknown cause: A prospective cohort study

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    Introduction: Diagnostic evaluation of patients with a bleeding tendency remains challenging, as no disorder is identified in approximately 50% of patients. An impaired interplay of several haemostatic factors might explain bleeding phenotype in these patients. Objective: To investigate whether global haemostasis assays are able to identify haemostatic abnormalities in patients with a bleeding tendency unexplained by current diagnostic laboratory tests. Materials and methods: Patients of ≥12 years with a bleeding tendency were included from a tertiary outpatient clinic. Bleeding phenotype was assessed with the ISTH-BAT. Patients were classified as having bleeding of unknown cause (BUC) or a mild bleeding disorder (MBD) based on abnormalities assessed by routine haemostatic tests. Global haemostasis tests (rotational thromboelastometry (ROTEM), thrombin generation test (TG) and plasma clot lysis time (CLT)) were measured in all patients. The results were compared with 76 controls. Results: One hundred and eighty-one patients were included, and 60% (109/181) was classified as having BUC. BUC patients demonstrated a significantly prolonged lag time in TG (median 7.7 minutes, IQR 6.7-8.7) and a significantly prolonged CLT (median 60.5 minutes, IQR 54.7-66.1) compared to controls. No differences in ROTEM variables were found. Patients with MBD showed an impaired thrombin generation with a significantly decreased ETP (median 1024 nmol/L*min, IQR 776-1355) and peak height (median 95 nmol/L, IQR 76-138), compared to BUC patients and controls. Conclusion: No major differences were found in ROTEM and TG variables in BUC patients compared to controls. BUC patients did have a significantly prolonged clot lysis time. The underlying mechanism for this finding is unknown

    Land use mix and physical activity in middle-aged and older adults: a longitudinal study examining changes in land use mix in two Dutch cohorts

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    Background: With urbanization and aging increasing in coming decades, societies face the challenge of keeping aging populations active. Land use mix (LUM) has been associated with cycling and walking, but whether changes in LUM relate to changes in cycling/walking is less known. Objectives: Our objective was to study the effect of LUM on cycling/walking in two Dutch aging cohorts using data with 10 years of follow-up. Methods: Data from 1183 respondents from the Health and Living Conditions of the Population of Eindhoven and Surroundings (GLOBE) study and 918 respondents from the Longitudinal Aging Study Amsterdam (LASA) were linked to LUM in 1000-m sausage network buffers at three time-points. Cycling/walking outcomes were harmonized to include average minutes spent cycling/walking per week. Data was pooled and limited to respondents that did not relocate between follow-up waves. Associations between LUM and cycling/walking were estimated using a Random Effects Within-Between (REWB) model that allows for the estimation of both within and between effects. Sensitivity analyses were performed on smaller (500-m) and larger (1600-m) buffers. Results: We found evidence of between-individual associations of LUM in 1000-m buffers and walking (β: 11.10, 95% CI: 0.08; 21.12), but no evidence of within-associations in 1000-m buffers. Sensitivity analyses using 500-m buffers showed similar between-associations, but negative within-associations (β: -35.67, 95% CI: − 68.85; − 2.49). We did not find evidence of between-individual associations of LUM in any buffer size and cycling, but did find evidence of negative within-associations between LUM in 1600-m buffers and cycling (β: -7.49, 95% CI: − 14.31; − 0.66). Discussion: Our study found evidence of positive associations between LUM and average walking time, but also some evidence of negative associations between a change in LUM and cycling/walking. LUM appears to be related to cycling/walking, but the effect of changes in LUM on cycling/walking is unclear

    A model for estimating the health economic impact of earlier diagnosis of chronic thromboembolic pulmonary hypertension

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    Background Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life-years (QALYs) and healthcare costs.Material and methods A Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC - VUmc, which is a Dutch CTEPH referral center. Medication costs were based on a mix of standard medication regimens.Results For 63-year-old CTEPH patients with a 14-month diagnostic delay of CTEPH (median age and delay of patients in the European CTEPH Registry), lifelong healthcare costs were estimated at EUR 117100 for a mix of treatment options. In a hypothetical scenario of maximal reduction of current delay, improved survival was estimated at a gain of 3.01 life-years and 2.04 QALYs. The associated cost increase was EUR 44654, of which 87% was due to prolonged medication use. This accounts for an incremental cost-utility ratio of EUR 21900/QALY.Conclusion Our constructed model based on the Dutch healthcare setting demonstrates a substantial health gain when CTEPH is diagnosed earlier. According to Dutch health economic standards, additional costs remain below the deemed acceptable limit of EUR 50000/QALY for the particular disease burden. This model can be used for evaluating cost-effectiveness of diagnostic strategies aimed at reducing the diagnostic delay.Analysis and support of clinical decision makin

    Prevalence, Treatment, and Prognosis of Tumor Thrombi in Renal Cell Carcinoma

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    BACKGROUND Renal cell carcinoma (RCC) can be complicated by a venous tumor thrombus (TT), of which the optimal management is unknown.OBJECTIVES This study sought to assess the prevalence of TT in RCC, its current management, and its association with venous thromboembolism (VTE), arterial thromboembolism (ATE), major bleeding (MB), and mortality.METHODS Patients diagnosed with RCC between 2010 and 2019 in our hospital were included and followed from RCC diagnosis until 2 years after, or until an outcome of interest (VTE, ATE, and MB) or death occurred, depending on the analysis. Cumulative incidences were estimated with death as a competing risk. Cause-specific hazard models were used to identify predictors and the prognostic impact.RESULTS Of the 647 patients, 86 had a TT (prevalence 13.3%) at RCC diagnosis, of which 34 were limited to the renal vein, 37 were limited to the inferior vena cava below the diaphragm, and 15 extended above the diaphragm; 20 patients started therapeutic anticoagulation and 45 underwent thrombectomy with/without anticoagulation. During follow-up (median 24.0 [IQR: 7.0-24.0] months), 17 TT patients developed a VTE, 0 developed an ATE, and 11 developed MB. TT patients were more often diagnosed with VTE (adjusted HR: 6.61; 95% CI: 3.18-13.73) than non-TT patients, with increasing VTE risks in more proximal TT levels. TT patients receiving anticoagulation still developed VTE (HR: 0.56; 95% CI: 0.13-2.48), at the cost of more MB events (HR: 3.44; 95% CI: 0.95-12.42) compared with those without anticoagulation.CONCLUSIONS Patients with RCC-associated TT were at high risk of developing VTE. Future studies should establish which of these patients benefit from anticoagulation therapy. (c) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
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