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  • Muller, David C., et al. (författare)
  • Circulating high sensitivity C reactive protein concentrations and risk of lung cancer : : Nested case-control study within Lung Cancer Cohort Consortium
  • 2019
  • Ingår i: BMJ (Online). - BMJ Publishing Group. - 0959-8146. ; 364
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. ParticiPants 5299 patients with incident lung cancer, with individually incidence density matched controls. exPOsure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main OutcOMe Measure Incident lung cancer diagnosis. results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. cOnclusiOns Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.
  • Osterhaus, Albert, et al. (författare)
  • Control and eradication of classic swine fever in wild boar
  • 2009
  • Ingår i: EFSA Journal. - 1831-4732. ; :1
  • Tidskriftsartikel (refereegranskat)abstract
    • Classical swine fever (CSF) is a disease that has been causing major socio-economic damages in the EU during the last decades. Although considerable progress has been made in the eradication and prevention of the disease, the threat for an epidemic still exists. The virus is endemic in the wild boar population of several member states (MS). Wild boar cannot be managed as domestic pigs. Hunting and vaccination have been tentatively used in order to stop transmission by reducing the number of susceptibles. Oral vaccination of wild boar with modified live vaccine based on the C-strain (the only suitable) is used; this vaccine does not allow serological differentiation between vaccinated and infected animals. The aim of the control measures for CSF in wild boar is to reduce the risk of transmission to domestic pigs, to prevent an &ldquo;endemic phase evolution&rdquo; or to reduce the endemic phase duration. In order to support and to improve the control and eradication measures as regards CSF in wild boar, EFSA was requested by the Commission to provide scientific advice on the efficacy of the available surveillance, hunting and vaccination measures to control and eradicate CSF in feral pig populations (wild boar), considering the possible use of new diagnostic tests and vaccines. In order to reply to the mandate data were collected from MS through two questionnaires (CSF vaccines, hunting practices and CSF vaccination in wild boar). Data were also extracted from the EU CSF wild boar data base, after requesting permission from the participating MS. Considering that the data received were rather limited and not comparable, the WG decided to use a model in order to fill the gaps in the available knowledge. For the evaluation of the efficacy of CSF control in wild boar a continuous metapopulation compartmental model developed in an EU research project (FP6-5015599-CSFVACCINE&amp;WILDBOAR) was applied. Although the disease manifests in the same manner in both domestic pig and wild boar it is more difficult to identify in wild boar because clinical monitoring of these is hardly possible. Wild boar found dead constitutes the main alert sign of CSF. Hunters and gamekeepers should be instructed to report the finding of each dead wild boar to the competent authority at all times. In case of high-risk situations, a passive surveillance should be complemented by an active serological surveillance. The active sampling of wild boar is not as efficient as in domestic pigs considering that hunting is the sole practical system to obtain samples and that the aim of hunting is quite different. Consequently, the sample size is not controlled by authorities and fits rarely the aim of the survey in terms of detecting the presence of disease at a certain level. In addition, the interpretation of serological results is confounded by maternal derived antibodies (until the 6th month of age), vaccination and the sampling quality. There is no definition at EU level of spatial and temporal units for surveillance, neither for criteria defining a disease free wild boar population. The sample size is not the only factor that dictates the overall sensitivity of surveillance systems. Indeed, wild boar habitat, hunting patterns, and disease distribution should be included when assessing surveillance system sensitivity. After a vaccination campaign, PCR positive animals can be due to modified live vaccines (MLV) but these MLV-vaccinated animals can be cross-checked for wild type CSF virus (genetic DIVA &ndash; discriminatory PCR). A positive PCR diagnosis should be considered to indicate that an animal is or has been infected with the wild type or MLV virus but it is not necessarly still infectious. According to previous field experience and to model simulations of a CSF epidemic in a wild boar population and the possible outcomes regarding vaccination: the disease will fade out without any additional control measures in small populations (between 1000 and 1500); hunting is not efficient for CSF control and should not exceed the normal 45% per year. Hunting is currently needed for sampling; vaccination: increases population immunity progressively. The maximum population immunity is only reached after three double campaigns; by one isolated campaign cannot increase population immunity adequately to control CSF and might even aggravate the persistence of CSF; mainly prevents the spread of the infection in neighbouring vaccinated patches; promotes long-term eradication through a progressive reduction of virus transmission to neighbouring areas; always reduces the epidemic peak (number of infected animals/time). Endemic evolution of infection may occur when a low rate of vaccination is achieved; in both infected and not yet infected areas, reaching a minimum target of 40 % of susceptible animals is necessary to obtain a positive control effect, below 20% - will increase probability of endemic stability, above 60% - will always eradicate the infection
  • Ricci, Cristian, et al. (författare)
  • Alcohol intake in relation to non-fatal and fatal coronary heart disease and stroke : : EPIC-CVD case-cohort study
  • 2018
  • Ingår i: BMJ (Online). - BMJ Publishing Group. - 0959-8146. ; 361
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To investigate the association between alcohol consumption (at baseline and over lifetime) and non-fatal and fatal coronary heart disease (CHD) and stroke. Design Multicentre case-cohort study. Setting A study of cardiovascular disease (CVD) determinants within the European Prospective Investigation into Cancer and nutrition cohort (EPIC-CVD) from eight European countries. Participants 32 549 participants without baseline CVD, comprised of incident CVD cases and a subcohort for comparison. Main outcome measures Non-fatal and fatal CHD and stroke (including ischaemic and haemorrhagic stroke). Results There were 9307 non-fatal CHD events, 1699 fatal CHD, 5855 non-fatal stroke, and 733 fatal stroke. Baseline alcohol intake was inversely associated with non-fatal CHD, with a hazard ratio of 0.94 (95% confidence interval 0.92 to 0.96) per 12 g/day higher intake. There was a J shaped association between baseline alcohol intake and risk of fatal CHD. The hazard ratios were 0.83 (0.70 to 0.98), 0.65 (0.53 to 0.81), and 0.82 (0.65 to 1.03) for categories 5.0-14.9 g/day, 15.0-29.9 g/day, and 30.0-59.9 g/day of total alcohol intake, respectively, compared with 0.1-4.9 g/day. In contrast, hazard ratios for non-fatal and fatal stroke risk were 1.04 (1.02 to 1.07), and 1.05 (0.98 to 1.13) per 12 g/day increase in baseline alcohol intake, respectively, including broadly similar findings for ischaemic and haemorrhagic stroke. Associations with cardiovascular outcomes were broadly similar with average lifetime alcohol consumption as for baseline alcohol intake, and across the eight countries studied. There was no strong evidence for interactions of alcohol consumption with smoking status on the risk of CVD events. Conclusions Alcohol intake was inversely associated with non-fatal CHD risk but positively associated with the risk of different stroke subtypes. This highlights the opposing associations of alcohol intake with different CVD types and strengthens the evidence for policies to reduce alcohol consumption.
  • Sahoo, Ranjit Kumar, et al. (författare)
  • Evolution of Hypolimnas butterflies (Nymphalidae) : Out-of-Africa origin and Wolbachia-mediated introgression
  • 2018
  • Ingår i: Molecular Phylogenetics and Evolution. - Elsevier. - 1055-7903. ; 123, s. 50-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypolimnas butterflies (Nymphalidae), commonly known as eggflies, are a popular model system for studying a wide range of ecological questions including mimicry, polymorphism, wing pattern evolution, and Wolbachia-host interactions. The lack of a time-calibrated phylogeny for this group has precluded understanding its evolutionary history. We reconstruct a species-level phylogeny using a nine gene dataset and estimate species divergence times. Based on the resulting tree, we investigate the taxon's historical biogeography, examine the evolution of host plant preferences, and test the hypothesis that the endosymbiotic bacterium Wolbachia mediates gene transfer between species. Our analyses indicate that the species are grouped within three strongly supported, deeply divergent clades. However, relationships among these three clades are uncertain. In addition, many Hypolimnas species are not monophyletic or monophyletic with weak support, suggesting widespread incomplete lineage sorting and/or introgression. Biogeographic analysis strongly indicates that the genus diverged from its ancestor in Africa and subsequently dispersed to Asia; the strength of this result is not affected by topological uncertainties. While the larvae of African species feed almost exclusively on Urticaceae, larvae of species found further east often feed on several additional families. Interestingly, we found an identical mitochondrial haplotype in two Hypolimnas species, H. bolina and H. alimena, and a strong association between this mitotype and the Wolbachia strain wBol1a. Future investigations should explore the plausibility of Wolbachia-mediated introgression between species.
  • Sasamoto, Naoko, et al. (författare)
  • Predicting circulating CA125 levels among healthy premenopausal women
  • 2019
  • Ingår i: Cancer Epidemiology Biomarkers and Prevention. - American Association for Cancer Research. - 1055-9965. ; 28:6, s. 1076-1085
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. Methods: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (-35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). Results: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r= 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). Conclusions: We identified a combination of factors associated with CA125 levels in premenopausal women. Impact: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.
  • Sathanoori, Ramasri, et al. (författare)
  • Shear stress modulates endothelial KLF2 through activation of P2X4.
  • 2015
  • Ingår i: Purinergic Signalling. - Springer. - 1573-9546. ; 11:1, s. 139-153
  • Tidskriftsartikel (refereegranskat)abstract
    • Vascular endothelial cells that are in direct contact with blood flow are exposed to fluid shear stress and regulate vascular homeostasis. Studies report endothelial cells to release ATP in response to shear stress that in turn modulates cellular functions via P2 receptors with P2X4 mediating shear stress-induced calcium signaling and vasodilation. A recent study shows that a loss-of-function polymorphism in the human P2X4 resulting in a Tyr315>Cys variant is associated with increased pulse pressure and impaired endothelial vasodilation. Although the importance of shear stress-induced Krüppel-like factor 2 (KLF2) expression in atheroprotection is well studied, whether ATP regulates KLF2 remains unanswered and is the objective of this study. Using an in vitro model, we show that in human umbilical vein endothelial cells (HUVECs), apyrase decreased shear stress-induced KLF2, KLF4, and NOS3 expression but not that of NFE2L2. Exposure of HUVECs either to shear stress or ATPγS under static conditions increased KLF2 in a P2X4-dependent manner as was evident with both the receptor antagonist and siRNA knockdown. Furthermore, transient transfection of static cultures of human endothelial cells with the Tyr315>Cys mutant P2X4 construct blocked ATP-induced KLF2 expression. Also, P2X4 mediated the shear stress-induced phosphorylation of extracellular regulated kinase-5, a known regulator of KLF2. This study demonstrates a major physiological finding that the shear-induced effects on endothelial KLF2 axis are in part dependent on ATP release and P2X4, a previously unidentified mechanism.
  • Smith, Todd, et al. (författare)
  • Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies
  • 2019
  • Ingår i: Gut. - BMJ Publishing Group Ltd. - 0017-5749. ; 68, s. 672-683
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.DESIGN: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability).RESULTS: The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC.CONCLUSION: Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
  • Ward, Heather A., et al. (författare)
  • Measured adiposity in relation to head and neck cancer risk in the European Prospective Investigation into Cancer and Nutrition
  • 2017
  • Ingår i: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. - American Association for Cancer Research. - 1538-7755. ; 26:6, s. 895-904
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer (HNC). However, most studies have used self-reported anthropometry which is prone to error.METHODS: Among 363 094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of HNC. HNC risk was examined in relation to body mass index (BMI) [lean: < 22.5 kg/m2, normal weight (reference): 22.5-24.9 kg/m2, overweight 25-29.9 kg/m2, obese: > 30 kg/m2], waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR) using Cox proportional hazards models.RESULTS: Among men, a BMI < 22.5 kg/m2 was associated with higher HNC risk [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.23 - 2.12)]; BMI was not associated with HNC among women. WC and WHR were associated with greater risk of HNC among women, (WC per 5 cm: HR 1.08, 95% CI 1.02 - 1.15; WHR per 0.1 unit: HR 1.64, 95% CI 1.38 - 1.93). After stratification by smoking status, the association for WHR was present only among smokers (p interaction 0.004). Among men, WC and WHR were associated with HNC only upon additional adjustment for BMI (WC per 5 cm: HR 1.16, 95% CI 1.07 - 1.26; WHR per 0.1 unit: HR 1.42, 95% CI 1.21 - 1.65).CONCLUSION: Central adiposity, particularly among women, may have a stronger association with HNC risk than previously estimated.IMPACT: Strategies to reduce obesity may beneficially impact HNC incidence.
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