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Abstract Background Recently a proof-of-concept was proposed to derive the soccer players’ individual in-situ acceleration-speed (AS) profile from global positioning system (GPS) data collected over several sessions and games. The present study aimed to propose an automatized method of individual GPS-derived in-situ AS profiling in a professional rugby union setting. Method AS profiles of forty-nine male professional rugby union players representing 61.5 million positions, from which acceleration was derived from speed during 51 training sessions and 11 official games, were analyzed. A density-based clustering algorithm was applied to identify outlier points. Multiple AS linear relationships were modeled for each player and session, generating numerous theoretical maximal acceleration (A 0 ), theoretical maximal running speed (S 0 ) and AS slope (AS slope, i.e., overall orientation of the AS profile). Each average provides information on the most relevant value while the standard deviation denotes the method accuracy. In order to assess the reliability of the AS profile within the data collection period, data were compared over two 2-week phases by the inter-class correlation coefficient. A 0 and S 0 between positions and type of sessions (trainings and games) were compared using ANOVA and post hoc tests when the significant threshold had been reached. Results All AS individual profiles show linear trends with high coefficient of determination (r2 > 0.81). Good reliability (Inter-class Correlation Coefficient ranging from 0.92 to 0.72) was observed between AS profiles, when determined 2 weeks apart for each player. AS profiles depend on players’ positions, types of training and games. Training and games data highlight that highest A 0 are obtained during games, while greatest S 0 are attained during speed sessions. Conclusions This study provides individual in-situ GPS-derived AS profiles with automatization capability. The method calculates an error of measurement for A 0 and S 0 , of paramount importance in order to improve their daily use. The AS profile differences between training, games and playing positions open several perspectives for performance testing, training monitoring, injury prevention and return-to-sport sequences in professional rugby union, with possible transferability to other sprint-based sports. Key Points AS profiles computed from rugby union GPS data provide positional benchmarks during training and competition. This study provides automatic detection of atypical data and the computation of error measurement of theoretical maximal acceleration and speed components. This refinement constitutes a step forward for a daily use of ecological data by considering data collection and method reliabilities. This easy-to-implement approach may facilitate its use to the performance management process (talent identification, training monitoring and individualization, return-to-sport).

Background: The characterization of the different pathophysiological mechanisms involved in normotensive versus hypertensive acute heart failure (AHF) might help to develop individualized treatments. Methods: The extent of hemodynamic cardiac stress and cardiomyocyte injury was quantified by measuring the B-type natriuretic peptide (BNP), N-terminal proBNP (NT-proBNP), and high-sensitivity cardiac troponin T (hs-cTnT) concentrations in 1152 patients presenting with centrally adjudicated AHF to the emergency department (ED) (derivation cohort). AHF was classified as normotensive with a systolic blood pressure (SBP) of 90–140 mmHg and hypertensive with SBP > 140 mmHg at presentation to the ED. Findings were externally validated in an independent AHF cohort (n = 324). Results: In the derivation cohort, with a median age of 79 years, 43% being women, 667 (58%) patients had normotensive and 485 (42%) patients hypertensive AHF. Hemodynamic cardiac stress, as quantified by the BNP and NT-proBNP, was significantly higher in normotensive as compared to hypertensive AHF [1105 (611–1956) versus 827 (448–1419) pg/mL, and 5890 (2959–12,162) versus 4068 (1986–8118) pg/mL, both p < 0.001, respectively]. Similarly, the extent of cardiomyocyte injury, as quantified by hs-cTnT, was significantly higher in normotensive AHF as compared to hypertensive AHF [41 (24–71) versus 33 (19–59) ng/L, p < 0.001]. A total of 313 (28%) patients died during 360 days of follow-up. All-cause mortality was higher in patients with normotensive AHF vs. patients with hypertensive AHF (hazard ratio 1.66, 95%CI 1.31–2.10; p < 0.001). Normotensive patients with a high BNP, NT-proBNP, or hs-cTnT had the highest mortality. The findings were confirmed in the validation cohort. Conclusion: Biomarker profiling revealed a higher extent of hemodynamic stress and cardiomyocyte injury in patients with normotensive versus hypertensive AHF.

Faire l’expérience de la grâce ne serait-il pas le véritable but de l’artiste, créateur ou interprète ? Nous tenterons d’y répondre à la lumière de la théorie du duende de Lorca qui, en mettant l’accent sur le caractère insaisissable et intraduisible de l’expérience artistique, questionne les limites de l’interprétation scientifique de l’art. Dans cette nuit du langage retrouvée, la musique peut provoquer des moments de grâce et d’intuition unifiée comme en témoignent les artistes et penseurs cités ici qui tentent d’approcher le mystère de la création artistique. Dans un monde où tout se mesure, reconnaître l’existence d’un incommensurable dans l’art et dans la musique en particulier est urgent aujourd’hui, tant sur le plan poétique que politique ; cela fait de la grâce un concept éthique, éloigné de toute volonté esthétique. Libératrice de forces vitales, elle prend appui sur le corps vivant pour découvrir des profondeurs inconnues d’où surgit une altérité qui le déborde et lui résiste mais dont la présence est constitutive de tout art véritable. En tant que jeu avec les forces (contraires) la musique fait coexister et résonner ensemble tous les éléments de cette lutte en un moment de grâce recherché par l’interprète dans sa création en acte.

Workplace literacy practices constitute the basis of today’s increasingly textualised work life. Due to the legislation on trade secrets, less research has been conducted on literacy practices in the private sector. This interview study of reported literacy practices focused on the soft-ware, dictionaries and other technologies used in writing tasks in 11 different businesses in Finland. The informants (n=18) were Swedish-speaking Finns working in the Helsinki area and in Vaasa. The study showed that office software (Word, Excel, PowerPoint) is used for writing, as is email clients, chats and messaging systems. When encountering difficulties in writing, asking a colleague for help is a frequent strategy, together with searching the internet using Google. More established dictionaries, glossaries, and synonym web sites are also used, but to a lesser extent. The findings suggest implications for teaching at different levels: students could be trained in complex and multilingual text production, to efficiently use the widely used office software and to assess content in free dictionaries and on similar websites from a linguistic point of view.

Abstract In Alzheimer’s disease and related tauopathies, trans-synaptic transfer and accumulation of pathological tau from donor to recipient neurons is thought to contribute to disease progression, but the underlying mechanisms are poorly understood. Using complementary in vivo and in vitro models, we examined the relationship between these two processes and neuronal clearance. Accumulation of p62 (a marker of defective protein clearance) correlated with pathological tau accumulation in two mouse models of tauopathy spread; Entorhinal Cortex-tau (EC-Tau) mice where tau pathology progresses in time from EC to other brain regions, and PS19 mice injected with tau seeds. In both models and in several brain regions, p62 colocalized with human tau in a pathological conformation (MC1 antibody). In EC-Tau mice, p62 accumulated before overt tau pathology had developed and was associated with the presence of aggregation-competent tau seeds identified using a FRET-based assay. Furthermore, p62 accumulated in the cytoplasm of neurons in the dentate gyrus of EC-Tau mice prior to the appearance of MC1 positive tauopathy. However, MC1 positive tau was shown to be present at the synapse and to colocalize with p62 as shown by immuno electron microscopy. In vitro, p62 colocalized with tau inclusions in two primary cortical neuron models of tau pathology. In a three-chamber microfluidic device containing neurons overexpressing fluorescent tau, seeding of tau in the donor chamber led to tau pathology spread and p62 accumulation in both the donor and the recipient chamber. Overall, these data are in accordance with the hypothesis that the accumulation and trans-synaptic spread of pathological tau disrupts clearance mechanisms, preceding the appearance of obvious tau aggregation. A vicious cycle of tau accumulation and clearance deficit would be expected to feed-forward and exacerbate disease progression across neuronal circuits in human tauopathies.

Organ injury and impairment are commonly observed in patients with acute heart failure (AHF), and congestion is an essential pathophysiological mechanism of impaired organ function. Congestion is the predominant clinical profile in most patients with AHF; a smaller proportion presents with peripheral hypoperfusion or cardiogenic shock. Hypoperfusion further deteriorates organ function. The injury and dysfunction of target organs (i.e. heart, lungs, kidneys, liver, intestine, brain) in the setting of AHF are associated with increased risk for mortality. Improvement in organ function after decongestive therapies has been associated with a lower risk for post-discharge mortality. Thus, the prevention and correction of organ dysfunction represent a therapeutic target of interest in AHF and should be evaluated in clinical trials. Treatment strategies that specifically prevent, reduce or reverse organ dysfunction remain to be identified and evaluated to determine if such interventions impact mortality, morbidity and patient-centred outcomes. This paper reflects current understanding among experts of the presentation and management of organ impairment in AHF and suggests priorities for future research to advance the field.

El artículo se centra en la noción de orquesta participativa (OP), que reúne a músicos y no músicos de todas las edades y orígenes para crear un sonido común. Esencialmente inclusiva, la OP permite practicar la escucha y la empatía experimentando con nuevas formas de convivencia, incluso en los lugares de marginalidad de nuestras sociedades contemporáneas (prisiones). Nos preguntamos en el artículo por el significado de la música en la vida humana, como arte no verbal y lenguaje sensorial; su importancia en la educación, centrada hoy más en la lógica racional como fundamento de la vida mental al servicio de la economía de mercado y no en la sensibilidad y la imaginación, los valores dominantes del ser humano. Mostraremos cómo el desarrollo de la conciencia musical puede ser un proceso educativo a través de la participación como fuerza social y expresión de una sensibilidad que la música moldea despertando el deseo de aprender. Lo que conduce a la emancipación, el verdadero objetivo de la educación.

Abstract Aims This study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor‐15 (GDF‐15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock. Methods and results Patients (n = 219) from the multicentre CardShock study were grouped according to age (elderly ≥75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP‐SHOCK II score to predict in‐hospital mortality and the additional value of GDF‐15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P

Abstract Alterations to cell polarization or to intercellular junctions are often associated with epithelial cancer progression, including breast cancers (BCa). We show here that the loss of the junctional scaffold protein MAGI1 is associated with bad prognosis in luminal BCa, and promotes tumorigenesis. E-cadherin and the actin binding scaffold AMOTL2 accumulate in MAGI1 deficient cells which are subjected to increased stiffness. These alterations are associated with low YAP activity, the terminal Hippo-pathway effector, but with an elevated ROCK and p38 Stress Activated Protein Kinase activities. Blocking ROCK prevented p38 activation, suggesting that MAGI1 limits p38 activity in part through releasing actin strength. Importantly, the increased tumorigenicity of MAGI1 deficient cells is rescued in the absence of AMOTL2 or after inhibition of p38, demonstrating that MAGI1 acts as a tumor-suppressor in luminal BCa by inhibiting an AMOTL2/p38 stress pathway.

Abstract Background Acute kidney injury (AKI) is a frequent form of organ injury in cardiogenic shock. However, data on AKI markers such as plasma proenkephalin (P-PENK) and neutrophil gelatinase-associated lipocalin (P-NGAL) in cardiogenic shock populations are lacking. The objective of this study was to assess the ability of P-PENK and P-NGAL to predict acute kidney injury and mortality in cardiogenic shock. Results P-PENK and P-NGAL were measured at different time points between baseline and 48 h in 154 patients from the prospective CardShock study. The outcomes assessed were AKI defined by an increase in creatinine within 48 h and all-cause 90-day mortality. Mean age was 66 years and 26% were women. Baseline levels of P-PENK and P-NGAL (median [interquartile range]) were 99 (71–150) pmol/mL and 138 (84–214) ng/mL. P-PENK > 84.8 pmol/mL and P-NGAL > 104 ng/mL at baseline were identified as optimal cut-offs for AKI prediction and independently associated with AKI (adjusted HRs 2.2 [95% CI 1.1–4.4, p = 0.03] and 2.8 [95% CI 1.2–6.5, p = 0.01], respectively). P-PENK and P-NGAL levels at baseline were also associated with 90-day mortality. For patients with oliguria 6 h before study enrollment, 90-day mortality differed significantly between patients with low and high P-PENK/P-NGAL at baseline (5% vs. 68%, p 105.7 pmol/L and P-NGAL24h > 151 ng/mL had unadjusted hazard ratios of 5.6 (95% CI 3.1–10.7, p

Abstract Focused ultrasound and microbubble (FUS + MB)-mediated blood–brain barrier (BBB) permeability enhancement can facilitate targeted brain-drug delivery. While controlling the magnitude of BBB permeability enhancement is necessary to limit tissue damage, little work has attempted to decouple these concepts. This work investigated the relationship between BBB permeability enhancement and the relative transcription of inflammatory mediators 4 h following sonication. Three microbubble formulations, Definity, BG8774, and MSB4, were compared, with the dose of each formulation normalized to gas volume. While changes in the transcription of key proinflammatory mediators, such as Il1b, Ccl2, and Tnf, were correlated to the magnitude of BBB permeability enhancement, these correlations were not independent of microbubble formulation; microbubble size distribution may play an important role, as linear regression analyses of BBB permeability magnitude versus differential gene expression for these proinflammatory mediators revealed significantly greater slopes for MSB4, a monodisperse microbubble with mean diameter of 4 μm, compared to Definity or BG8774, both polydisperse microbubbles with mean diameters below 2 μm. Additionally, the function of an acoustic feedback control algorithm, based on the detection threshold of ultraharmonic emissions, was assessed. While this control strategy was effective in limiting both wideband emissions and red blood cell extravasation, microbubble formulation was found to influence the magnitude of BBB leakage and correlations to acoustic emissions. This work demonstrates that while the initial magnitude of FUS + MB-mediated BBB permeability enhancement has a clear influence on the subsequent inflammatory responses, microbubble characteristics influence these relationships and must also be considered.

In this article we present results from a case study of five business professionals and their workplace literacy practices and literacy events. The five interviewees are Swedish-speaking Finns, part of a 5 % minority in Finland, and they live both in the Helsinki capital area and in the Vaasa region. The business professionals work for two anonymized companies: Delta, a global business consultant company, and Zeta, a Scandinavian bank. Our theoretical framework is New literacy studies (Barton 2007/1994). All the interviewees use at least three languages at their work: their mother tongue Swedish, their second language Finnish (both are national languages in Finland), and English. High skills of both national languages are needed to perform the work tasks, and national languages are used more than English. The writing tasks are diverse and connected to the specialized work tasks of each employee, with the exception of e-mails that all interviewees write daily. The language choices are influenced by several factors, among them the language preferences of the recipient and the task at hand. Evidently, the companies have managed to make the best use of the language skills of the interviewees.

We analyse the stochastic properties of the 49 pulsars that comprise the first International Pulsar Timing Array (IPTA) data release. We use Bayesian methodology, performing model selection to determine the optimal description of the stochastic signals present in each pulsar. In addition to spin-noise and dispersion-measure (DM) variations, these models can include timing noise unique to a single observing system, or frequency band. We show the improved radio-frequency coverage and presence of overlapping data from different observing systems in the IPTA data set enables us to separate both system and band-dependent effects with much greater efficacy than in the individual pulsar timing array (PTA) data sets. For example, we show that PSR J1643-1224 has, in addition to DM variations, significant band-dependent noise that is coherent between PTAs which we interpret as coming from time-variable scattering or refraction in the ionized interstellar medium. Failing to model these different contributions appropriately can dramatically alter the astrophysical interpretation of the stochastic signals observed in the residuals. In some cases, the spectral exponent of the spin-noise signal can vary from 1.6 to 4 depending upon the model, which has direct implications for the long-term sensitivity of the pulsar to a stochastic gravitational-wave (GW) background. By using a more appropriate model, however, we can greatly improve a pulsar's sensitivity to GWs. For example, including system and band-dependent signals in the PSR J0437-4715 data set improves the upper limit on a fiducial GW background by ~60 per cent compared to a model that includes DM variations and spin-noise only.

Abstract Aims Insulin‐like growth factor binding protein‐4 (IGFBP‐4) fragments have been shown to predict the risk of major adverse cardiovascular events, including segment‐elevation myocardial infarction, in patients with acute coronary syndrome. We evaluated the prognostic value of the carboxy‐terminal fragment of IGFBP‐4 (CT‐IGFBP‐4) for all‐cause mortality in emergency room patients with acute heart failure (AHF). Methods and results CT‐IGFBP‐4, N‐terminal pro brain natriuretic peptide (NT‐proBNP), and C‐reactive protein (CRP) were measured at admission from the lithium‐heparin plasma of 156 patients with AHF. All‐cause mortality was recorded for 1 year. Receiver operator characteristic (ROC) curves, Kaplan–Meier, and Cox proportional hazard ratio analyses were performed to evaluate the prognostic value of the various clinical variables, CT‐IGFBP‐4, NT‐proBNP, CRP, and their combinations. During 1 year of follow‐up, 52 (33.3%) patients died. CT‐IGFBP‐4 only weakly correlated with NT‐proBNP (Pearson correlation coefficient r = 0.16, P = 0.044) and did not correlate with CRP (r = 0.08, P = 0.35), emphasizing the different nature of these biomarkers. The receiver operator characteristic area under the curve (ROC AUC) of CT‐IGFBP‐4 for the prediction of all‐cause mortality (0.727) was significantly higher than that of NT‐proBNP (0.680, P = 0.045) and CRP (0.669, P = 0.016). The combination of CT‐IGFBP‐4, NT‐proBNP, and CRP predicted mortality significantly better (ROC AUC = 0.788) than any of the biomarkers alone (P

Abstract Aims Urgent revascularization is the mainstay of treatment in acute coronary syndrome (ACS) related cardiogenic shock (CS). The aim was to investigate the association of angiographic results with 90‐day mortality. Procedural complications of percutaneous coronary intervention (PCI) were also examined. Methods and results This CardShock (NCT01374867) substudy included 158 patients with ACS aetiology and data on coronary angiography and complications during PCI procedure. Survival analysis was conducted with Kaplan–Meier curves and Cox regression analysis. Median age was 67 ± 11 years, and 77% were men. During 90‐day follow‐up, 66 (42%) patients died. Patients with one‐vessel disease (n = 49) had lower mortality than patients with two‐vessel (n = 59) or three‐vessel (n = 50) disease (25% vs. 48% vs. 52%, P = 0.011). Successful revascularization [Thrombolysis in Myocardial Infarction (TIMI) Flow 3 post‐PCI) was achieved more often in survivors than non‐survivors (81% vs. 60%, P = 0.019). The median symptom‐to‐balloon time was 340 (196–660) minutes, with no difference between survivors and non‐survivors. In multivariable mortality analysis, multivessel disease (HR 2.59, CI95% 1.29–5.18) and TIMI flow

El objetivo es mostrar cómo la orquesta puede ser un lugar de educación capaz de devolver la confianza y la autoestima a los detenidos y mejorar la convivencia en las cárceles. El estudio se basa en la metodología de investigación-acción (cualitativa-cuantitativa) y de investiga ción-creación para mostrar que los valores aprendidos en la orquesta (escucha, responsabilidad, disciplina, solidaridad, convivencia) son aplicables en la vida y pueden iniciar procesos de transforma ción introduciéndose entre sí en nuevas posibilidades que facilitan la reintegra ción a la vida social. En el contexto de las prisiones francesas, caracterizadas hoy por un hacinamiento creciente que genera conflictos y violencia, o el de las prisiones venezolanas donde estos problemas son recurrentes, la creación de orquestas es un proyecto político, dirigido a establecer un espacio común y personal donde los dete nidos puedan interactuar en estos lugares separación y fragmentación de los espacios y tiempos. En conclusión, la educación no puede tener lugar sin la creación de un ambiente de convivencia (en el sentido dado por el movimiento internacional de Convivencia) donde se afirman los principios de individualiza ción y oposición creativa, que están en la base de cualquier democracia, así como la orquesta concebida como una micro-so ciedad.

Explaining the emergence and maintenance of intratumor heterogeneity is an important question in cancer biology. Tumor cells can generate considerable subclonal diversity, which influences tumor growth rate, treatment resistance, and metastasis, yet we know remarkably little about how cells from different subclones interact. Here, we confronted two murine mammary cancer cell lines to determine both the nature and mechanisms of subclonal cellular interactions in vitro. Surprisingly, we found that, compared to monoculture, growth of the “winner” was enhanced by the presence of the “loser” cell line, whereas growth of the latter was reduced. Mathematical modeling and laboratory assays indicated that these interactions are mediated by the production of paracrine metabolites resulting in the winner subclone effectively “farming” the loser. Our findings add a new level of complexity to the mechanisms underlying subclonal growth dynamics.

IntroductionMyocardial hemorrhage (IMH) and persistent microvascular obstruction (MVO) are associated with impaired myocardial recovery and adverse clinical outcomes in STEMI patients. However, their relationship with circulating inflammatory biomarkers is unclear in human patients.Methods and resultsTwenty consecutive patients referred for primary percutaneous coronary intervention of first STEMI were included in a prospective study. Blood sampling was performed at admission, 4, 12, 24, 48 hours, 7 and 30 days after reperfusion for inflammatory biomarker (C reactive protein, fibrinogen, interleukin-6 (IL-6) and neutrophils count) assessment. At seven days, cardiovascular magnetic resonance (CMR) was performed for infarct size, MVO and IMH assessment. Median infarct size was 24.6% Interquartile range (IQR) [12.0-43.5] of LV mass and edema was 13.2% IQR [7.7-36.1] of LV mass. IL-6 reached a peak at H24 (5.6 pg/mL interquartile range (IQR) [2.5-17.5]), CRP at H48 (11.7 mg/L IQR [7.1-69.2]), fibrinogen one week after admission (4.4 g/L IQR [3.8-6.7]) and neutrophils at H12 (9.0 G/L IQR [6.5-12.7]). MVO was present in 11 patients (55% of the study population) and hemorrhage in 7 patients (35%). Patients with IMH had significantly higher IL-6, CRP, fibrinogen, and neutrophils levels compared to patients without IMH. Patients with persistent MVO had significantly higher CRP, fibrinogen and neutrophils level compared to patients without MVO, but identical IL-6 kinetics.ConclusionIn human patients with acute myocardial infarction, intramyocardial hemorrhage appears to have a stronger relationship with inflammatory biomarker release compared to persistent MVO. Attenuating myocardial hemorrhage may be a novel target in future adjunctive STEMI treatments.

BackgroundEndometriosis is associated with increased risk of clear cell ovarian cancer and has even suggested being an etiological factor for this cancer. Association between endometriosis and extraovarian clear cell cancers is unclear. This study aimed to assess the association between surgically diagnosed endometriosis and risk of extraovarian clear cell cancers according to the type of endometriosis (i.e., ovarian, peritoneal, and other endometriosis) and the site of clear cell cancer.MethodsIn this register-based historic cohort study we identified all women with surgically diagnosed endometriosis from the Finnish Hospital Discharge Registry 1987-2012. Data on extraovarian clear cell cancers of these women were obtained from the Finnish Cancer Registry. The follow-up started January 1st, 2007 or at endometriosis diagnosis (if later), and ended at emigration, death or on the December 31st, 2014. Standardized incidence ratios were calculated for each site of clear cell carcinoma (intestine, kidney, urinary tract, gynecological organs other than ovary), using the Finnish female population as reference.ResultsThe endometriosis cohort consisted of 48,996 women, including 22,745 women with ovarian and 19,809 women with peritoneal endometriosis. Altogether 23 extraovarian clear cell cancers were observed during 367,386 person-years of follow-up. The risk of extraovarian clear cell cancer was not increased among all women with surgically diagnosed endometriosis (standardized incidence ratio 0.89, 95% confidence interval 0.56-1.33) nor in different types of endometriosis. The incidence of clear cell cancer in any specific site was not increased either.ConclusionsThe risk of extraovarian clear cell cancers in women with surgically diagnosed endometriosis is similar to that in the general population in Finland.

Exposure to hepatitis C virus (HCV) typically results in chronic infection that leads to progressive liver disease ranging from mild inflammation to severe fibrosis and cirrhosis as well as primary liver cancer. HCV triggers innate immune signaling within the infected hepatocyte, a first step in mounting of the adaptive response against HCV infection. Persistent inflammation is strongly associated with liver tumorigenesis. The goal of our work was to investigate the initiation of the inflammatory processes triggered by HCV viral proteins in their host cell and their possible link with HCV-related liver cancer. We report a dramatic upregulation of the lymphotoxin signaling pathway and more specifically of lymphotoxin-β in tumors of the FL-N/35 HCV-transgenic mice. Lymphotoxin expression is accompanied by activation of NF-κB, neosynthesis of chemokines and intra-tumoral recruitment of mononuclear cells. Spectacularly, IKKβ inactivation in FL-N/35 mice drastically reduces tumor incidence. Activation of lymphotoxin-β pathway can be reproduced in several cellular models, including the full length replicon and HCV-infected primary human hepatocytes. We have identified NS5B, the HCV RNA dependent RNA polymerase, as the viral protein responsible for this phenotype and shown that pharmacological inhibition of its activity alleviates activation of the pro-inflammatory pathway. These results open new perspectives in understanding the inflammatory mechanisms linked to HCV infection and tumorigenesis.