External validity of clinical trials with diverse trastuzumab-based chemotherapy regimens in advanced gastroesophageal adenocarcinoma: data from the AGAMENON-SEOM registry

Quimioteràpia; Càncer gàstric; TrastuzumabQuimioterapia; Cáncer gástrico; TrastuzumabChemotherapy; Gastric cancer; TrastuzumabBackground: Trastuzumab combined with cisplatin and fluoropyrimidines, either capecitabine or 5-fluorouracile (XP/FP), is the standard first-line treatment for advanced, HER2-positive, gastric cancer patients based on the ToGA trial. Despite the lack of phase III trials, many clinicians administer trastuzumab with alternative regimens. One meta-analysis suggests that substituting cisplatin for oxaliplatin might lead to greater efficacy and less toxicity. Methods: 594 patients with HER2-positive gastroesophageal adenocarcinoma were recruited from the AGAMENON-SEOM registry. The objective was to evaluate the external validity of clinical trials with chemotherapy and trastuzumab. Results: The regimens used in at least 5% of the patients were XP (27%), oxaliplatin and capecitabine (CAPOX) (26%), oxaliplatin and 5-fluorouracil (FOLFOX) (14%), FP (14%), triplet with anthracycline/docetaxel (7%), and carboplatin-FU (5%). Median exposure to trastuzumab was longer with FOLFOX (11.4 months, 95% CI, 9.1–21.0) versus ToGA regimens (7.5, 6.4–8.5), p < 0.001. Patients with HER2-IHC 3+ cancers had higher response rates than those with IHC 2+/FISH+, odds-ratio 1.97 (95% CI, 1.25–3.09). The results achieved with CAPOX–trastuzumab were comparable to those attained with ToGA regimens. FOLFOX–trastuzumab was superior to ToGA schemes in terms of overall survival (OS), with a greater magnitude of effect in IHC 2+/FISH+ tumors (HR 0.47, 0.24–0.92) compared with IHC 3+ (HR 0.69, 0.49–0.96), and in diffuse (HR 0.37, 0.20–0.69) versus intestinal-type tumors (HR 0.76, 0.54–1.06). Conclusion: We have updated the external validity of clinical trials with trastuzumab in first-line treatment of gastric cancer. Our data confirm the comparable outcomes of ToGA regimens and CAPOX–trastuzumab in clinical practice and point toward a possible benefit of FOLFOX–trastuzumab, contingent on the subtypes typically less sensitive to trastuzumab, to be confirmed in clinical trials.The authors received no financial support for the research, authorship, and/or publication of this article

Air radon equilibrium factor measurement in a Waste Water Pre-Treatment Plant

[EN] We analyze in this paper a Waste Water Pre-Treatment Plant (WWTP) located at the Mediterranean coast with air radon concentration above Spanish action level (600 Bq per cubic meter). This paper presents a method for radon equilibrium determination by gamma spectrometry measuring of the radon progeny concentrations in the air, in order to estimate WWTP workers effective dose more exactly. The method is based on simultaneous sampling of air through a filter paper and alpha spectrometry measurement of radon activity concentration in the air. According to the measured radon activity concentration in the air of 368 +/- 45 Bq/m(3) the equilibrium factor between radon and progenies is estimated to be F=0.27, which is in good agreement with expected values.Martinez-Ferri, JE.; Juste Vidal, BJ.; Ortiz Moragón, J.; Martorell Alsina, SS.; Verdú Martín, GJ. (2017). Air radon equilibrium factor measurement in a Waste Water Pre-Treatment Plant. Radiation Physics and Chemistry. 140:20-24. doi:10.1016/j.radphyschem.2017.03.011S202414

A vision about lifelong learning and its barriers

Around 25 years ago, some researchers argued for moving towards innovative learning models characterized by being more personalized and where the students would have a more active role in deciding what to learn, when to learn and how to learn. Nowadays, there is a need for a flexible, efficient, universal and lifelong education. Lifelong learning is fully integrated into our society and, from the student point of view, it is very different from regular learning. Among these differences there is the maturity of students, the fact that the domains of interest are much broader, the way how learning occurs at different depths, the fact that the topics to study may be related both to work, family and leisure, and that students have little availability due to their necessity to conciliate home, work, leisure and learning. Lifelong learning requires personalized models that adapt to students'' needs and constraints, but lifelong learners keep suffering from models that are neither adapted to their necessities, nor to the needs of society. This paper reflects on the actual situation of lifelong learning, analyses some of the relevant literature and discusses the challenges to conceptualize, from a transdisciplinary point of view, innovative e-learning models that promote self-determination of students

Developing a novelty method to estimate Radon doses in a Waste Water pre-Treatment Plant

[EN] According to World Health Organization (WHO), the radon is the second leading cause of lung cancer. This work is centered on a Waste Water Pre-Treatment Plant (WWTP) with radon concentration above Spanish action level (600 Bq per cubic meter). The authors have developed a novelty method based on gamma and alpha spectrometry to measure the radon equilibrium factor. At the same time, a Matlab (c) algorithm (UPVDose) has been coded based on the International Commission on Radiological Protection (ICRP) 66 Human Respiratory Tract Model for Radiological Protection (HRT), to calculate the inhalation doses received by workers of this treatment plant due to the radon progeny. The effective doses of the workers obtained in the human respiratory tract are found to be low, but results are very dependent on the radionuclide type of absorptionMartinez-Ferri, JE.; Juste Vidal, BJ.; Verdú Martín, GJ.; Miró Herrero, R.; Ortiz Moragón, J.; Martorell Alsina, SS. (2019). Developing a novelty method to estimate Radon doses in a Waste Water pre-Treatment Plant. Radiation Physics and Chemistry. 155:323-327. https://doi.org/10.1016/j.radphyschem.2018.09.009S323327155Durridge Radon Instrumentation, 2015. RAD 7 Radon Detector, user manual. DURRIDGE Company 〈https://durridge.com/products/rad7-radon-detector/〉.Forkapić, S., Mrđa, D., Vesković, M., Todorović, N., Bikit, K., Nikolov, J., Hansman, J., 2012. Radon equilibrium measurement in the air. In: Proceedings of the Paper Presented at First East European Radon Symposium–FERAS.Zhu, H., Li, J., Qiu, R., Pan, Y., Wu, Z., Li, C., & Zhang, H. (2018). Establishment of detailed respiratory tract model and Monte Carlo simulation of radon progeny caused dose. Journal of Radiological Protection, 38(3), 990-1012. doi:10.1088/1361-6498/aac987Marsh, J. W., Laurier, D., & Tirmarche, M. (2017). RADON DOSIMETRY FOR WORKERS: ICRP’S APPROACH. Radiation Protection Dosimetry, 177(4), 466-474. doi:10.1093/rpd/ncx065Martinez, J. E., Juste, B., Ortiz, J., Martorell, S., & Verdu, G. (2017). Air radon equilibrium factor measurement in a Waste Water Pre-Treatment Plant. Radiation Physics and Chemistry, 140, 20-24. doi:10.1016/j.radphyschem.2017.03.011Ramola, R. C., Prasad, M., Kandari, T., Pant, P., Bossew, P., Mishra, R., & Tokonami, S. (2016). Dose estimation derived from the exposure to radon, thoron and their progeny in the indoor environment. Scientific Reports, 6(1). doi:10.1038/srep31061Sánchez, G., & Rodríguez-Díaz, J. M. (2006). Optimal design and mathematical model applied to establish bioassay programs. Radiation Protection Dosimetry, 123(4), 457-463. doi:10.1093/rpd/ncl49

Spanish Preanalytical Quality Monitoring Program (SEQC), an overview of 12 years' experience

Preanalytical variables, such as sample collection, handling and transport, may affect patient results. Preanalytical phase quality monitoring should be established in order to minimize laboratory errors and improve patient safety. A retrospective study (2001-2013) of the results obtained through the Spanish Society of Clinical Biochemistry and Molecular Pathology (SEQC) External quality assessment (preanalytical phase) was performed to summarize data regarding the main factors affecting preanalytical phase quality. Our aim was to compare data from 2006 to 2013 with a previously published manuscript assessing the 2001-2005 period. A significant decrease in rejection rates was observed both for blood and urine samples. For serum samples, the most frequent rejection causes in the first period were non-received samples (37.5%), hemolysis (29.3%) and clotted samples (14.4%). Conversely, in the second period, hemolysis was the main rejection cause (36.2%), followed by non-received samples (34.5%) and clotted samples (11.1%). For urine samples, the main rejection cause overall was a non-received sample (up to 86.1% of cases in the second period, and 81.6% in the first). For blood samples with anticoagulant, the number of rejections also decreased. While plasma-citrate-ESR still showed the highest percentages of rejections (0.980% vs. 1.473%, p<0.001), the lowest corresponded to whole-blood EDTA (0.296% vs. 0.381%, p<0.001). For the majority of sample types, a decrease in preanalytical errors was confirmed. Improvements in organization, implementation of standardized procedures in the preanalytical phase, and participation in a Spanish external quality assessment scheme may have notably contributed to error reduction in this phase

The physical oceanography of the transport of floating marine debris

Marine plastic debris floating on the ocean surface is a major environmental problem. However, its distribution in the ocean is poorly mapped, and most of the plastic waste estimated to have entered the ocean from land is unaccounted for. Better understanding of how plastic debris is transported from coastal and marine sources is crucial to quantify and close the global inventory of marine plastics, which in turn represents critical information for mitigation or policy strategies. At the same time, plastic is a unique tracer that provides an opportunity to learn more about the physics and dynamics of our ocean across multiple scales, from the Ekman convergence in basin-scale gyres to individual waves in the surfzone. In this review, we comprehensively discuss what is known about the different processes that govern the transport of floating marine plastic debris in both the open ocean and the coastal zones, based on the published literature and referring to insights from neighbouring fields such as oil spill dispersion, marine safety recovery, plankton connectivity, and others. We discuss how measurements of marine plastics (both in situ and in the laboratory), remote sensing, and numerical simulations can elucidate these processes and their interactions across spatio-temporal scales

Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways

Recurrent respiratory tract infections (RRTIs) are the first leading cause of community-and nosocomial-acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is highly demanded. Daily sublingual administration of the whole heat-inactivated polybacterial preparation (PBP) MV130 significantly reduced the rate of respiratory infections in RRTIs patients, however, the immunological mechanisms of action remain unknown. Herein, we study the capacity of MV130 to immunomodulate the function of human dendritic cells (DCs) as a potential mechanism that contribute to the clinical benefits. We demonstrate that DCs from RRTIs patients and healthy controls display similar ex vivo immunological responses to MV130. By combining systems biology and functional immunological approaches we show that MV130 promotes the generation of Th1/Th17 responses via receptor-interacting serine/threonine-protein kinase-2 (RIPK2)-and myeloid-differentiation primary-response gene88 (MyD88)-mediated signalling pathways under the control of IL-10. In vivo BALB/c mice sublingually immunized with MV130 display potent systemic Th1/Th17 and IL-10 responses against related and unrelated antigens. We elucidate immunological mechanisms underlying the potential way of action of MV130, which might help to design alternative treatments in other clinical conditions with high risk of recurrent infections.This work was supported by grant IPT-2012-0639-090000 from INNPACTO and MINECO, Spain to Inmunotek S.L. The authors' laboratories are supported by grants SAF2014-52706-R to O.P. from MINECO, Spain, and SAF2016-79040R to D.S. from MINECO and European Fund for Regional Development, Spain. O.P. is a Ramon y Cajal Scholar funded by MINECO and the European Social Fund. L.C. is a recipient of a European Respiratory Society Fellowship (RESPIRE2-2013-3708). We thank to Juan Lopez-Relano and Sarai Martinez-Cano for excellent technical assistance with mice experiments.S

Correction to: A Phase II Study Evaluating Combined Neoadjuvant Cetuximab and Chemotherapy Followed by Chemoradiotherapy and Concomitant Cetuximab in Locoregional Oesophageal Cancer Patients

Errors were subsequently identified in the article and the following corrections should be note

Secreted factors as synaptic organizers

A critical step in synaptic development is the differentiation of presynaptic and postsynaptic compartments. This complex process is regulated by a variety of secreted factors that serve as synaptic organizers. Specifically, fibroblast growth factors, Wnts, neurotrophic factors and various other intercellular signaling molecules are proposed to regulate presynaptic and/or postsynaptic differentiation. Many of these factors appear to function at both the neuromuscular junction and in the central nervous system, although the specific function of the molecules differs between the two. Here we review secreted molecules that organize the synaptic compartments and discuss how these molecules shape synaptic development, focusing on mammalian in vivo systems. Their critical role in shaping a functional neural circuit is underscored by their possible link to a wide range of neurological and psychiatric disorders both in animal models and by mutations identified in human patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79160/1/j.1460-9568.2010.07338.x.pd

SARS-CoV-2 Catalonia contact tracing program : evaluation of key performance indicators

Background: Guidance on SARS-CoV-2 contact tracing indicators have been recently revised by international public health agencies. The aim of the study is to describe and analyse contact tracing indicators based on Catalonia's (Spain) real data and proposing to update them according to recommendations. Methods: Retrospective cohort analysis including Catalonia's contact tracing dataset from 20 May until 31 December 2020. Descriptive statistics are performed including sociodemographic stratification by age, and differences are assessed over the study period. Results: We analysed 923,072 contacts from 301,522 SARS-CoV-2 cases with identified contacts (67.1% contact tracing coverage). The average number of contacts per case was 4.6 (median 3, range 1-243). A total of 403,377 contacts accepted follow-up through three phone calls over a 14-day quarantine period (84.5% of contacts requiring follow-up). The percentage of new cases declared as contacts 14 days prior to diagnosis evolved from 33.9% in May to 57.9% in November. All indicators significantly improved towards the target over time (p < 0.05 for all four indicators). Conclusions: Catalonia's SARS-CoV-2 contact tracing indicators improved over time despite challenging context. The critical revision of the indicator's framework aims to provide essential information in control policies, new indicators proposed will improve system delay's follow-up. The study provides information on COVID-19 indicators framework experience from country's real data, allowing to improve monitoring tools in 2021-2022. With the SARS-CoV-2 pandemic being so harmful to health systems and globally, is important to analyse and share contact tracing data with the scientific community