Efficacy and safety of the combination of pravastatin and sorafenib for the treatment of advanced hepatocellular carcinoma (ESTAHEP clinical trial)

Pravastatin has demonstrated anti-tumor activity in preclinical and clinical studies. This multicentric randomized double-blind placebo-controlled phase II study (NCT01418729) investigated the efficacy and safety of sorafenib + pravastatin combination on the overall survival (OS) and time to progression (TTP) of patients with advanced hepatocellular carcinoma (aHCC). A total of 31 patients were randomized. Median OS did not differ between both groups (12.4 months for the sorafenib + pravastatin group vs. 11.6 months for the control group). Of note, however, the radiological TTP was higher in patients treated with sorafenib + pravastatin than in the control group (9.9 months vs. 3.2 months; p = 0.008). Considering all the study population, the presence of portal vein thrombosis (PVT) was associated with worse OS, being lower in patients with PVT compared to patients without PVT (6.3 months vs. 14.8 months; p = 0.026). Data also showed a decrease in OS in patients with vascular invasion (VI) compared to patients who did not present it (6.3 months vs. 14.8 months; p = 0.041). The group of patients without dermatological events (DE) showed lower OS (6.9 months vs. 14.5 months; p = 0.049). In conclusion, combination of sorafenib + pravastatin was safe and well-tolerated, prolonging the TTP of patients with aHCC but not improving the OS compared to sorafenib + placebo. The absence of PVT and VI and the development of DE are positive prognostic factors of sorafenib response

Acoustically driven arrayed waveguide grating

We demonstrate compact tunable phased-array wavelength-division multiplexers driven by surface acoustic waves (SAWs) in the low GHz range. The devices comprise two couplers, which respectively split and combine the optical signal, linked by an array of single-mode waveguides (WGs). Two different layouts are presented, in which multi-mode interference couplers or free propagating regions were separately employed as couplers. The multiplexers operate on five equally distributed wavelength channels, with a spectral separation of 2 nm. A standing SAW modulates the refractive index of the arrayed WGs. Each wavelength component periodically switches paths between the output channel previously asigned by the design and the adjacent channels, at a fixed applied acoustic power. The devices were monolithically fabricated on (Al,Ga)As. A good agreement between theory and experiment is achieved

Assessment of Haemodynamic Remodeling in Fetal Aortic Coarctation Using a Lumped Model of the Circulation

Introduction: Aortic coarctation is one of the most difficult cardiac defects to diagnose before birth, and it accounts for 8% of congenital heart diseases. Antenatal diagnosis is crucial for early treatment of the neonate and to decrease the risk of morbidity and mortality; however the fetal hemodynamic changes are not fully understood and current imaging methods are limited to accurately diagnosis this congenital defect. Objective: We propose to use a lumped model of the fetal circulation to provide insights into the hemodynamic changes in fetuses with aortic coarctation, and thus helping to improve its diagnosis. Methods: To achieve this goal a patient-specific lumped model of the fetal circulation was implemented in OpenCOR, including the modeling of different types and degrees of aortic coarctation. A parametric study of degree and type of coarctation was performed, where blood flow distribution, cerebroplacental ratio, pressure drop over the coarctation and left ventricular pressure were quantified. Results: Obvious changes in the fetal hemodynamics were observed only from 80% of coarctation, corresponding to the clinically used cut-off for pressure drop of 20 mmHg. Furthermore, the observed hemodynamic changes were different depending on the location and degree of the coarctation

"Invisible burials" and fragmentation practices in Iron Age Europe:Excavations at the Monte Bernorio Necropolis (Northern Spain)

The scarcity of burial remains in large parts of Iron Age Europe, particularly in the Atlantic regions, has often led scholars to discuss the apparent “invisibility” of graves. This paper presents the results from several excavation campaigns at Monte Bernorio, one of the most important sites of the 1st millennium b.c. on the Iberian Peninsula. The fieldwork and post-excavation work carried out in the area of the necropolis have identified numerous burial pits, with complex ritual activities characterized by fragmentation and the practice of the pars pro toto. In addition, evidence for later rituals in some of the graves can be linked to ancestor worship. The results provide important insights into funerary practices in Late Iron Age Europe, leading us to rethink the very meaning of cemeteries in the study area and beyond.- Burial Traditions in Iron Age Europe - The Monte Bernorio Archaeological Zone - The 2007–2008 Necropolis Excavations - The 2015–2016 Necropolis Excavations - Post-Excavation Work and Interpretation: The Faunal and Human Remains - Structure and Chronology of Monte Bernorio Area 7 - Destruction of the Body, Commemoration in the Absence of a Corpse, and Visibility of the Mortuary Rite

Species mixing reduces drought susceptibility of Scots pine (Pinus sylvestris L.) and oak (Quercus robur L., Quercus petraea (Matt.) Liebl.) – Site water supply and fertility modify the mixing effect

Tree species mixing has been widely promoted as a promising silvicultural tool for reducing drought stress. However, so far only a limited number of species combinations have been studied in detail, revealing inconsistent results. In this study, we analysed the effect of mixing Scots pine and oak (pedunculate oak and sessile oak) trees on their drought response along a comprehensive ecological gradient across Europe. The objective was to improve our knowledge of general drought response patterns of two fundamental European tree species in mixed versus monospecific stands. We focused on three null hypotheses: () tree drought response does not differ between Scots pine and oak, () tree drought response of Scots pine and oak is not affected by stand composition (mixture versus monoculture) and () tree drought response of Scots pine and oak in mixtures and monocultures is not modified by tree size or site conditions. To test the hypotheses, we analysed increment cores of Scots pine and oak, sampled in mixed and monospecific stands, covering a wide range of site conditions. We investigated resistance (the ability to maintain growth levels during drought), recovery (the ability to restore a level of growth after drought) and resilience (the capacity to recover to pre-drought growth levels), involving site-specific drought events that occurred between 1976 and 2015. In monocultures, oak showed a higher resistance and resilience than Scots pine, while recovery was lower. Scots pine in mixed stands exhibited a higher resistance, but also a lower recovery compared with Scots pine in monocultures. Mixing increased the resistance and resilience of oak. Ecological factors such as tree size, site water supply and site fertility were found to have significant effects on the drought response. In the case of Scots pine, resistance was increased by tree size, while recovery was lowered. Resistance of oak increased with site water supply. The observed mixing effect on the tree drought response of Scots pine and oak was in some cases modified by the site conditions studied. Positive mixing effects in terms of resistance and resilience of oak increased with site water supply, while the opposite was found regarding recovery. In contrast, site fertility lessened the positive mixing effect on the resistance of Scots pine. We hypothesise that the observed positive mixing effects under drought mainly result from water- and/or light-related species interactions that improve resource availability and uptake according to temporal and spatial variations in environmental conditions.This work was supported by the European Union as part of the ERA-Net SUMFOREST project REFORM – Mixed species forest management. Lowering risk, increasing resilience (2816ERA02S, PCIN2017-026) and the Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 778322. All contributors thank their national funding institutions for supporting the establishment, mensuration and analysis of the studied triplets. The first author wants to thank the German Federal Ministry of Food and Agriculture (BMEL) for financial support through the Federal Office for Agriculture and Food (BLE) (grant number 2816ERA02S), as well as the Bayerische Staatsforsten (BaySF) and Landesbetrieb Forst Brandenburg for providing suitable research sites. Research on the Lithuanian triplets (LT 1, LT 2) was made possible by the national funding institution Research Council of Lithuania (LMTLT) (agreement number S-SUMFOREST-17-1). The French site FR 1 belongs to the OPTMix experimental site (https://optmix.irstea.fr), which is supported annually by Ecofor, Allenvi, and the French national research infrastructure ANAEE-F. A special thank is due to Peter Biber for supporting the statistical analysis

Mindfulness-based program for anxiety and depression treatment in healthcare professionals: A pilot randomized controlled trial

In primary health care, the work environment can cause high levels of anxiety and depression, triggering relevant expert and individual change. Mindfulness-Based Stress Reduction (MBSR) programs reduce signs of anxiety and depression. The purpose of this sub-analysis of the total project, was to equate the effectiveness of the standard MBSR curriculum with the abbreviated version in minimizing anxiety and depression. This randomized controlled clinical trial enrolled 112 mentors and resident specialists from Family and Community Medicine and Nurses (FCMN), distributed across six teaching units (TU) of the Spanish National Health System (SNHS). Experimental group participants received a MBRS training (abbreviated/standard). Depression and anxiety levels were measured with the Goldberg Anxiety and Depression Scale (GADS) at three different time periods during the analysis: before (pre-test) and after (post-test) participation, as well as 3 months after the completion of intervention. Taking into account the pre-test scores as the covariate, an adjusted analysis of covariance (ANCOVA) showed significant depletion in anxiety and depression in general (F (2.91) = 4.488; p = 0.014; ¿2 = 0.090) and depression in particular (F (2, 91) = 6.653; p = 0.002; ¿2 = 0.128 at the post-test visit, maintaining their effects for 3 months (F (2.79) = 3.031; p = 0.050; ¿2 = 0.071—F (2.79) = 2.874; p = 0.049; ¿2 = 0.068, respectively), which is associated with the use of a standard training program. The abbreviated training program did not have a significant effect on the level of anxiety and depression. The standard MBSR training program had a positive effect on anxiety and depression and promotes long-lasting effects in tutors and resident practitioners. New research is needed to demonstrate the effectiveness of abbreviated versions of training programs. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Follow-up with Telemedicine in Early Discharge for COPD Exacerbations: Randomized Clinical Trial (TELEMEDCOPD-Trial)

The results reported by different studies on telemonitoring in patients with chronic obstructive pulmonary disease (COPD) have been contradictory, without showing clear benefits to date. The objective of this study was to ascertain whether an early discharge and home hospitalization telehealth program for patients with COPD exacerbation is as effective as and more efficient than a traditional early discharge and home hospitalization program. A prospective experimental non-inferiority study, randomized into two groups (telemedicine/control) was conducted. The telemedicine group underwent monitoring and was required to transmit data on vital constants and ECGs twice per day, with a subsequent telephone call and 2 home visits by healthcare staff (intermediate and at discharge). The control group received daily visits. The main variable was time until first exacerbation. The secondary variables were: number of exacerbations; use of healthcare resources; satisfaction; quality of life; anxiety-depression; and therapeutic adherence, measured at one and 6 months of hospital discharge. A total of 116 patients were randomized (58 to each group) without significant differences in baseline characteristics or time until first exacerbation, i.e. median 48 days (pp. 25-75:23-120) in the control group, and 47 days (pp. 25-75:19-102) in the intervention group; p = 0.52). A significant decrease in the number of visits was observed in the intervention versus the control group, 3.8 ± 1 vs 5.1 ± 2(p = 0.001), without significant differences in the number of exacerbations. In conclusion follow-up via a telemedicine program in early discharge after hospitalization is as effective as conventional home follow up, being the cost of either strategy not significantly different.This study was awarded a Health Research Fund (Fondo de Investigaciones Sanitarias/FIS) grant, dossier No. PI12/01161 of the Carlos III Institute of Health and the Ministry of Sciences, Innovation and Universities.S

Primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy

Cancer complicates approximately 0.1% of all pregnancies. Primary tracheal carcinoma is one of very rarely seen tumors and the rate of its being seen makes up approximately % 0.2 of all tumors of respiratory tract. The patient, 28 years old, who has 28-weeks-pregnant, was diagnosed with primary tracheal adenocystic carcinoma. Patient was made operation as thoracotomy and tracheal tumor was removed at the 28th week of pregnancy. Patient was delivered with sectio abdominale at the 39th week of pregnancy. Primary tracheal adenocystic carcinoma is very rarely seen tumors and it is the first tracheal ACC with pregnancy case in literature to have been detected and surgically treated during pregnancy. We discussed primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy with literature

Modelling of spectral properties and population kinetics studies of inertial fusión and laboratory astrophysical plasmas

Fundamental research and modelling in plasma atomic physics continue to be essential for providing basic understanding of many different topics relevant to high-energy-density plasmas. The Atomic Physics Group at the Institute of Nuclear Fusion has accumulated experience over the years in developing a collection of computational models and tools for determining the atomic energy structure, ionization balance and radiative properties of, mainly, inertial fusion and laser-produced plasmas in a variety of conditions. In this work, we discuss some of the latest advances and results of our research, with emphasis on inertial fusion and laboratory-astrophysical applications

The albumin-bilirubin grade uncovers the prognostic relationship between hepatic reserve and immune dysfunction in HIV-associated hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of liver-related mortality in people living with HIV, where co-infection with hepatotropic viruses accelerates the course of chronic liver disease. AIM: To evaluate whether the albumin-bilirubin (ALBI) grade, a more accurate marker of liver dysfunction in HCC, might identify patients with progressive liver dysfunction in the context of HIV/hepatitis co-infection. METHODS: Using uni- and multi-variable analyses, we studied the albumin-bilirubin grade as a predictor of overall survival (OS) in a large, multi-center cohort of patients with HIV-associated HCC recruited from 44 centres in 9 countries within the Liver Cancer in HIV study group. Patients who underwent liver transplantation were excluded. RESULTS: A total of 387 patients, predominantly HCV co-infected (78%) with balanced representation of all Barcelona Clinic Liver Cancer (BCLC) stages (A = 33%, B = 18%, C = 37%, D = 12%) were recruited. At HCC diagnosis, 84% had been on anti-retrovirals for a median duration of 8.8 years. The albumin-bilirubin grade identified significant differences in median survival of 97 months for grade 1 (95% CI 13-180 months), 17 months for grade 2 (95% CI 11-22 months) and 6 months for grade 3 (95% CI 4-9 months, P < .001). A more advanced albumin-bilirubin grade correlated with lower CD4 counts (464/373/288 cells/mm3 for grades 1/2/3) and higher HIV viraemia (3.337/8.701/61.845 copies/mL for grades 1/2/3, P < .001). CONCLUSIONS: In this large, multi-center retrospective study, the albumin-bilirubin grade highlights the interplay between liver reserve and immune dysfunction as prognostic determinants in HIV-associated HCC