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Schematic view of the β-As2Te3 polymorph (S. G. R3̄m) including the polyhedral units (AsTe6, TeAS6, and Te2 antiprism of β-As2Te3) of the hexagonal unit cell. Images of the experimental and theoretical techniques used are shown as well as the main results reported.

An understudied morphosyntactic innovation, reanalysis of the Proto-Austronesian (PAn) stative intransitive prefix *ma- as a transitive affix, offers new insights into Austronesian higher-order subgrouping. Malayo-Polynesian is currently considered a primary branch of Austronesian, with no identifiably closer relationship with any linguistic subgroup in the homeland (Blust 1999, 2009/2013; Ross 2005). However, the fact that it displays the same innovative use of ma- with Amis, Siraya, Kavalan and Basay-Trobiawan and shares the merger of PAn *C/t with this group suggests that Malayo-Polynesian and East Formosan may share a common origin – the subgroup that comprises the four languages noted above. This observation points to a revised subgrouping more consistent with a socio-historical picture where the out-of-Taiwan population descended from a seafaring community expanding to the Batanes and Luzon after having developed a seafaring tradition. It also aligns with recent findings in archaeology and genetics that (i) eastern Taiwan is the most likely starting point of Austronesian dispersal (Hung 2005, 2008, 2019; Bellwood 2017; Bellwood & Dizon 2008; Carson & Hung 2018) and (ii) that the Amis bear a significantly closer relationship with Austronesian communities outside Taiwan (Capelli et al. 2001; Trejaut et al. 2005; McColl et al. 2018; Pugach et al. 2021; Tätte et al. 2021). Future investigation of additional shared innovations between Malayo-Polynesian and East Formosan could shed further light on their interrelationships.

Cancer; Drug development; Gene amplifications Cáncer; Desarrollo de fármacos; Amplificaciones de genes Càncer; Desenvolupament de medicaments; Amplificacions de gens The identification of novel therapeutic targets for specific cancer molecular subtypes is crucial for the development of precision oncology. In the last few years, CRISPR/Cas9 screens have accelerated the discovery and validation of new targets associated with different tumor types, mutations, and fusions. However, there are still many cancer vulnerabilities associated with specific molecular features that remain to be explored. Here, we used data from CRISPR/Cas9 screens in 954 cancer cell lines to identify gene dependencies associated with 16 common cancer genomic amplifications. We found that high-copy-number genomic amplifications generate multiple collateral dependencies within the amplified region in most cases. Further, to prioritize candidate targets for each chromosomal region amplified, we integrated gene dependency parameters with both druggability data and subcellular location. Finally, analysis of the relationship between gene expression and gene dependency led to the identification of genes, the expression of which may constitute predictive biomarkers of dependency. In conclusion, our study provides a set of druggable targets specific for each amplification, opening the possibility to specifically target amplified tumors on this basis. This research was funded by grants from Institut Català d’Oncologia (ICO), Instituto de Salud Carlos III (PI21/00640), AGAUR (2021 FI_B 00088), Fundació BOSCH, Iniciativa Tot per tu, Fundació Amics Joan Petit, and Mi compañero de viaje.

This joint experimental and theoretical study of the structural and vibrational properties of β-In2S3 upon compression shows that this tetragonal defect spinel undergoes two reversible pressure-induced order-disorder transitions up to 20 GPa. We propose that the first high-pressure phase above 5.0 GPa has the cubic defect spinel structure of α-In2S3 and the second high-pressure phase (ϕ-In2S3) above 10.5 GPa has a defect α-NaFeO2-type (R3m) structure. This phase, related to the NaCl structure, has not been previously observed in spinels under compression and is related to both the tetradymite structure of topological insulators and to the defect LiTiO2 phase observed at high pressure in other thiospinels. Structural characterization of the three phases shows that α-In2S3 is softer than β-In2S3 while ϕ-In2S3 is harder than β-In2S3. Vibrational characterization of the three phases is also provided, and their Raman-active modes are tentatively assigned. Our work shows that the metastable α phase of In2S3 can be accessed not only by high temperature or varying composition, but also by high pressure. On top of that, the pressure-induced β-α-ϕ sequence of phase transitions evidences that β-In2S3, a BIII2XV3 compound with an intriguing structure typical of AIIBIII2XVI4 compounds (intermediate between thiospinels and ordered-vacancy compounds) undergoes: (i) a first phase transition at ambient pressure to a disordered spinel-type structure (α-In2S3), isostructural with those found at high pressure and high temperature in other BIII2XV3 compounds; and (ii) a second phase transition to the defect α-NaFeO2-type structure (ϕ-In2S3), a distorted NaCl-type structure that is related to the defect NaCl phase found at high pressure in AIIBIII2XVI4 ordered-vacancy compounds and to the defect LiTiO2-type phase found at high pressure in AIIBIII2XVI4 thiospinels. This result shows that In2S3 (with its intrinsic vacancies) has a similar pressure behaviour to thiospinels and ordered-vacancy compounds of the AIIBIII2XVI4 family, making β-In2S3 the union link between such families of compounds and showing that group-13 thiospinels have more in common with ordered-vacancy compounds than with oxospinels and thiospinels with transition metals.

Prodefen® is a dietary food supplement formulated as a synbiotic that has shown additional benefit to the standard supportive therapy in the management of acute viral diarrhoea in children. There is scarce evidence of this synbiotic in adults. The objective of this randomised double blind placebo-controlled clinical trial was to evaluate the efficacy and safety of Prodefen Plus® in the prevention of antibiotic-associated diarrhoea (AAD) in an adult population requiring either antibiotic treatment for an oral infection or antibiotic prophylaxis for a dental surgical procedure in a dental consultation. 151 subjects were randomised to the active (synbiotic) or control arm (placebo) for 14 days. There was a significantly higher reduction in the AAD incidence, and an improvement in the stool consistency in the active group. A higher reduction in both the frequency and duration of the diarrhoea episodes in the active group was also observed, as it was an improved perception of the diarrhoea severity. Overall, the study medication was well tolerated. In conclusion, results from this study confirm the beneficial effect of the synbiotic administered as adjuvant therapy in preventing the antibiotic-associated diarrhoea.

J.M.O. acknowledges financial support from the Portuguese Foundation for Science and Technology (FCT) and the European Social Fund (ESF) through the PhD grant SFRH/BD/131700/2017. The work leading to these results has received funding from the European Research Council under the European Community's H2020 2014-2021 ERC grant Agreement nffi 669416 "Lucky Star". We thank S. Para who supported some travels to observe the 5 October 2017 occultation. T.B. was supported for this research by an appointment to the National Aeronautics and Space Administration (NASA) Post-Doctoral Program at the Ames Research Center administered by Universities Space Research Association (USRA) through a contract with NASA. We acknowledge useful exchanges with Mark Gurwell on the ALMA CO observations. This work has made use of data from the European Space Agency (ESA) mission Gaia (https://www.cosmos.esa.int/gaia), processed by the Gaia Data Processing and Analysis Consortium (DPAC, https://www.cosmos.esa.int/web/gaia/dpac/consortium).Funding for the DPAC has been provided by national institutions, in particular the institutions participating in the Gaia Multilateral Agreement. J.L.O., P.S.-S., N.M. and R.D. acknowledge financial support from the State Agency for Research of the Spanish MCIU through the "Center of Excellence Severo Ochoa" award to the Instituto de Astrofisica de Andalucia (SEV-2017-0709), they also acknowledge the financial support by the Spanish grant AYA-2017-84637-R and the Proyecto de Excelencia de la Junta de Andalucia J.A. 2012-FQM1776. The research leading to these results has received funding from the European Union's Horizon 2020 Research and Innovation Programme, under Grant Agreement no. 687378, as part of the project "Small Bodies Near and Far" (SBNAF). P.S.-S. acknowledges financial support by the Spanish grant AYA-RTI2018-098657-J-I00 "LEO-SBNAF". The work was partially based on observations made at the Laboratorio Nacional de Astrofisica (LNA), Itajuba-MG, Brazil. The following authors acknowledge the respective CNPq grants: F.B.-R. 309578/2017-5; R.V.-M. 304544/2017-5, 401903/2016-8; J.I.B.C. 308150/2016-3 and 305917/2019-6; M.A. 427700/20183, 310683/2017-3, 473002/2013-2. This study was financed in part by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior -Brasil (CAPES) -Finance Code 001 and the National Institute of Science and Technology of the e-Universe project (INCT do e-Universo, CNPq grant 465376/2014-2). G.B.R. acknowledges CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016 and CAPES-PRINT/UNESP grant 88887.571156/2020-00, M.A. FAPERJ grant E26/111.488/2013 and A.R.G.Jr. FAPESP grant 2018/11239-8. B.E.M. thanks CNPq 150612/2020-6 and CAPES/Cofecub-394/2016-05 grants. Part of the photometric data used in this study were collected in the frame of the photometric observations with the robotic and remotely controlled telescope at the University of Athens Observatory (UOAO; Gazeas 2016). The 2.3 m Aristarchos telescope is operated on Helmos Observatory by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. Observations with the 2.3 m Aristarchos telescope were carried out under OPTICON programme. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 730890. This material reflects only the authors views and the Commission is not liable for any use that may be made of the information contained therein. The 1. 2m Kryoneri telescope is operated by the Institute for Astronomy, Astrophysics, Space Applications and Remote Sensing of the National Observatory of Athens. The Astronomical Observatory of the Autonomous Region of the Aosta Valley (OAVdA) is managed by the Fondazione Clement Fillietroz-ONLUS, which is supported by the Regional Government of the Aosta Valley, the Town Municipality of Nus and the "Unite des Communes valdotaines Mont-Emilius". The 0.81 m Main Telescope at the OAVdA was upgraded thanks to a Shoemaker NEO Grant 2013 from The Planetary Society. D.C. and J.M.C. acknowledge funds from a 2017 'Research and Education' grant from Fondazione CRT-Cassa di Risparmio di Torino. P.M. acknowledges support from the Portuguese Fundacao para a Ciencia e a Tecnologia ref. PTDC/FISAST/29942/2017 through national funds and by FEDER through COMPETE 2020 (ref. POCI010145 FEDER007672). F.J. acknowledges Jean Luc Plouvier for his help. S.J.F. and C.A. would like to thank the UCL student support observers: Helen Dai, Elise Darragh-Ford, Ross Dobson, Max Hipperson, Edward Kerr-Dineen, Isaac Langley, Emese Meder, Roman Gerasimov, Javier Sanjuan, and Manasvee Saraf. We are grateful to the CAHA, OSN and La Hita Observatory staffs. This research is partially based on observations collected at Centro Astronomico HispanoAleman (CAHA) at Calar Alto, operated jointly by Junta de Andalucia and Consejo Superior de Investigaciones Cientificas (IAA-CSIC). This research was also partially based on observation carried out at the Observatorio de Sierra Nevada (OSN) operated by Instituto de Astrofisica de Andalucia (CSIC). This article is also based on observations made with the Liverpool Telescope operated on the island of La Palma by Liverpool John Moores University in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias with financial support from the UK Science and Technology Facilities Council. Partially based on observations made with the Tx40 and Excalibur telescopes at the Observatorio Astrofisico de Javalambre in Teruel, a Spanish Infraestructura Cientifico-Tecnica Singular (ICTS) owned, managed and operated by the Centro de Estudios de Fisica del Cosmos de Aragon (CEFCA). Tx40 and Excalibur are funded with the Fondos de Inversiones de Teruel (FITE). A.R.R. would like to thank Gustavo Roman for the mechanical adaptation of the camera to the telescope to allow for the observation to be recorded. R.H., J.F.R., S.P.H. and A.S.L. have been supported by the Spanish projects AYA2015-65041P and PID2019-109467GB-100 (MINECO/FEDER, UE) and Grupos Gobierno Vasco IT1366-19. Our great thanks to Omar Hila and their collaborators in Atlas Golf Marrakech Observatory for providing access to the T60cm telescope. TRAPPIST is a project funded by the Belgian Fonds (National) de la Recherche Scientifique (F.R.S.-FNRS) under grant PDR T.0120.21. TRAPPIST-North is a project funded by the University of Liege, and performed in collaboration with Cadi Ayyad University of Marrakesh. E.J. is a FNRS Senior Research Associate., Context. A stellar occultation by Neptune's main satellite, Triton, was observed on 5 October 2017 from Europe, North Africa, and the USA. We derived 90 light curves from this event, 42 of which yielded a central flash detection. Aims. We aimed at constraining Triton's atmospheric structure and the seasonal variations of its atmospheric pressure since the Voyager 2 epoch (1989). We also derived the shape of the lower atmosphere from central flash analysis. Methods. We used Abel inversions and direct ray-tracing code to provide the density, pressure, and temperature profiles in the altitude range similar to 8 km to similar to 190 km, corresponding to pressure levels from 9 mu bar down to a few nanobars. Results. (i) A pressure of 1.18 +/- 0.03 mu bar is found at a reference radius of 1400 km (47 km altitude). (ii) A new analysis of the Voyager 2 radio science occultation shows that this is consistent with an extrapolation of pressure down to the surface pressure obtained in 1989. (iii) A survey of occultations obtained between 1989 and 2017 suggests that an enhancement in surface pressure as reported during the 1990s might be real, but debatable, due to very few high S/N light curves and data accessible for reanalysis. The volatile transport model analysed supports a moderate increase in surface pressure, with a maximum value around 2005-2015 no higher than 23 mu bar. The pressures observed in 1995-1997 and 2017 appear mutually inconsistent with the volatile transport model presented here. (iv) The central flash structure does not show evidence of an atmospheric distortion. We find an upper limit of 0.0011 for the apparent oblateness of the atmosphere near the 8 km altitude., Portuguese Foundation for Science and Technology SFRH/BD/131700/2017, European Social Fund (ESF) SFRH/BD/131700/2017, European Research Council under the European Community's H2020 2014-2021 ERC grant 669416, Spanish Government SEV-2017-0709 AYA-2017-84637-R AYA-RTI2018-098657-J-I00, Junta de Andalucia 2012-FQM1776, European Union's Horizon 2020 Research and Innovation Programme, as part of the project "Small Bodies Near and Far" (SBNAF) 687378, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ), Fundacao de Apoio a Pesquisa do Distrito Federal (FAPDF) 309578/2017-5 304544/2017-5 401903/2016-8 308150/2016-3 305917/2019-6 427700/2018-3 310683/2017-3 473002/2013-2, Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) 001, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) 465376/2014-2 CAPES-FAPERJ/PAPDRJ grant E26/203.173/2016 CAPES-PRINT/UNESP grant 88887.571156/2020-00, Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio De Janeiro (FAPERJ) E26/111.488/2013, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) 2018/11239-8, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) 150612/2020-6, European Union's Horizon 2020 research and innovation programme 730890, Regional Government of the Aosta Valley, Town Municipality of Nus, Unite des Communes valdotaines Mont-Emilius, Planetary Society, Fondazione CRT-Cassa di Risparmio di Torino, Portuguese Foundation for Science and Technology PTDC/FISAST/29942/2017, FEDER through COMPETE 2020 POCI010145 FEDER007672, UK Research & Innovation (UKRI), Science & Technology Facilities Council (STFC), Fondos de Inversiones de Teruel (FITE), Spanish Government AYA2015-65041P PID2019-109467GB-100, Grupos Gobierno Vasco IT1366-19, Fonds de la Recherche Scientifique - FNRS PDR T.0120.21, University of Liege, CAPES/Cofecub-394/2016-05

O pectus excavatum é considerado uma patologia da parede torácica, onde há convexidade no aspecto ventral do esterno, o que gera complicações secundárias, como alongamento ventrodorsal do tórax e aumento da pressão intratorácica, entre outras. No presente caso, o corpo de um cachorro Buldogue Francês nasceu com sinais prévios de decaimento e baixo consumo de leito materno, além de uma avaliação médica forense. De acordo com a avaliação patológica, foi encontrada uma fenda no peito esternal relacionada às esternas caudais próximas à cartilagem xifóide, conteúdo espumoso na cartilagem epiglótica da laringe e sinais graves de enfisema nos lobos caudal, craniano e médio pulmonar. Na avaliação cardiológica, foi observada assimetria morfológica invaginante no septo interventricular na mesma área em que a fenda esternal ocorre, por sua vez, na avaliação radiográfica, evidencia uma depressão dorsal do terço caudal do esterno com alterações consideráveis na silhueta cardíaca. Na Colômbia não há relatos de ninhadas completas que apresentem esta alteração, portanto, pretende-se que este seja o primeiro relatório anatomopatológico e de imagem que descreva a patologia em caninos.

In this study, we report an experimental investigation of (Gd1−xYbx)2O3 under high pressure by means of Raman scattering measurements complemented with ab initio calculations in pure Gd2O3. Raman spectroscopy of compressed (Gd1−xYbx)2O3 (x = 0.11) revealed a first phase transition from the cubic Ia 3 phase (C-type) to the monoclinic C2/m phase (B-type) at 6.2 GPa followed by a second phase transition towards the trigonal P 3 m1 phase (A-type) at 9.8 GPa. This sequence of phase transitions is different to that previously reported for pure Gd2O3. A phase transition from the trigonal to the monoclinic phase is observed on downstroke, so the B-type phase remains metastable at room pressure, as observed in all C-type rare earth sesquioxides. Theoretical calculations have helped to identify the different polymorphs and to assign the symmetry of the observed first-order Raman-active modes in the three phases. The pressure coefficients of the Raman-active modes of the three phases followed under pressure have been reported and compared to those of pure Gd2O3 and other rare-earth sesquioxides.

Parallel Flash Talk at the "XIX International Workshop on Neutrino Telescopes" on line - 18-26 February, 2021

Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma (STS) in children and adolescents. In Spain the annual incidence is 4.4 cases per million children 14 years. It is an uncommon neoplasm in adults, but 40% of RMS are diagnosed in patients over 20 years of age, representing 1% of all STS in this age group. RMS can appear anywhere in the body, with some sites more frequently affected including head and neck, genitourinary system and limbs. Assessment of a patient with suspicion of RMS includes imaging studies (MRI, CT, PET-CT) and biopsy. All patients with RMS should receive chemotherapy, either at diagnosis in advanced or metastatic stages, or after initial resection in early local stages. Local control includes surgery and/or radiotherapy depending on site, stage, histology and response to chemotherapy. This guide provides recommendations for diagnosis, staging and treatment of this neoplasm.

Industry 4.0, also known as the “Fourth Industrial Revolution”, is currently transforming our society. As a consequence agriculture, industrial and service sectors are changing. In this context manufacturing companies have identified “Industry 4.0” as an opportunity to develop their competitiveness in their operations and organizational efficiency. Goal of this paper is to give a conceptual overview of the impact of new capabilities from the fourth Industrial Revolution on production and maintenance management tasks in order to provide an impulse to current manufacturing companies by providing recommendations on areas and tasks with higher potentials.

We report a joint experimental and theoretical study of the low-pressure phase of α'-Ga

We report a joint experimental and theoretical study of the low-pressure phase of α′-Ga2S3 under compression. Theoretical ab initio calculations have been compared to X-ray diffraction and Raman scattering measurements under high pressure carried out up to 17.5 and 16.1 GPa, respectively. In addition, we report Raman scattering measurements of α′-Ga2S3 at high temperature that have allowed us to study its anharmonic properties. To understand better the compression of this compound, we have evaluated the topological properties of the electron density, the electron localization function, and the electronic properties as a function of pressure. As a result, we shed light on the role of the Ga–S bonds, the van der Waals interactions inside the channels of the crystalline structure, and the single and double lone electron pairs of the sulphur atoms in the anisotropic compression of α′-Ga2S3. We found that the structural channels are responsible for the anisotropic properties of α′-Ga2S3 and the A′(6) phonon, known as the breathing mode and associated with these channels, exhibits the highest anharmonic behaviour. Finally, we report calculations of the electronic band structure of α′-Ga2S3 at different pressures and find a nonlinear pressure behaviour of the direct band gap and a pressure-induced direct-to-indirect band gap crossover that is similar to the behaviour previously reported in other ordered-vacancy compounds, including β-Ga2Se3. The importance of the single and, more specially, the double lone electron pairs of sulphur in the pressure dependence of the topmost valence band of α′-Ga2S3 is stressed., The authors thank the financial support from the Spanish Research Agency (AEI) under projects MALTA Consolider Team network (RED2018-102612-T) and projects MAT2016-75586-C4-2/3-P, FIS2017-83295-P, PID2019-106383GB-42/43, and PGC2018-097520-A-100, as well as from Generalitat Valenciana under Project PROMETEO/2018/123 (EFIMAT). A. M. and P. R.-H. acknowledge computing time provided by Red Espa?ola de Supercomputaci?n (RES) and MALTA-Cluster and E. L. D. S. acknowledges Marie Sklodowska-Curie Grant No. 785789-COMEX from the European Union's Horizon 2020 research and innovation program. J. A. S. also wants to thank the Ramon y Cajal fellowship (RYC-2015-17482) for financial support. We also thank the ALBA synchrotron light source for funded experiment 2017022088 at the MSPD-BL04 beamline.

[EN] Two anomalous broad bands are usually found in the Raman spectrum of bulk and 2D Te-based chalcogenides, which include binary compounds, like ZnTe, CdTe, HgTe, GaTe, GeTe, SnTe, PbTe, GeTe2, As2Te3, Sb2Te3, Bi2Te3, NiTe2, IrTe2, and TiTe2, as well as ternary compounds, like GaGeTe, SnSb2Te4, SnBi2Te4, and GeSb2Te5. Many different explanations have been proposed in the literature for the origin of the anomalous broad bands in tellurides, usually located between 119 and 145 cm(-1). They have been attributed to the intrinsic Raman modes of the sample, to oxidation of the sample, to the folding of Brillouin-edge modes onto the zone center, to the existence of a double resonance, like that of graphene, or to the formation of Te precipitates. In this paper, we provide arguments to demonstrate that such bands correspond to clusters or precipitates of trigonal Te in the form of nanosize or microsize grains or layers that are segregated either inside or at the surface of the samples. Several mechanisms for Te segregation are discussed and sample heating caused by excessive laser power during Raman scattering measurements is emphasized. Besides, we show that anomalous Raman modes related to Se precipitates also occur in selenides, thus providing a general vision for better characterization of selenides and tellurides by means of Raman scattering measurements and for a better understanding of chalcogenides in general., This work has been performed under financial support from the Spanish Ministry of Science, Innovation and Universities, the Spanish Research Agency (AEI), and the European Fund for Regional Development (FEDER) under grants TEC2017-85912C2-2, RED2018-102612-T (MALTA-CONSOLIDER TEAM network) and PID2019-106383 GB-C42/C43. We are also thankful for financial support from Generalitat Valenciana under grant PROMETEO/2018/123 (EFIMAT). The authors also acknowledge Dr Philipp Urban for performing the synthesis of SnBi2Te4.

Tinnitus is the perception of a phantom sound and the patient's reaction to it. Although much progress has been made, tinnitus remains a scientific and clinical enigma of high prevalence and high economic burden, with an estimated prevalence of 10%–20% among the adult population. The EU is funding a new collaborative project entitled “Unification of Treatments and Interventions for Tinnitus Patients” (UNITI, grant no. 848261) under its Horizon 2020 framework. The main goal of the UNITI project is to set the ground for a predictive computational model based on existing and longitudinal data attempting to address the question of which treatment or combination of treatments is optimal for a specific patient group based on certain parameters. Clinical, epidemiological, genetic and audiological data, including signals reflecting ear-brain communication, as well as patients' medical history, will be analyzed making use of existing databases. Predictive factors for different patient groups will be extracted and their prognostic relevance validated through a Randomized Clinical Trial (RCT) in which different patient groups will undergo a combination of tinnitus therapies targeting both auditory and central nervous systems. From a scientific point of view, the UNITI project can be summarized into the following research goals: (1) Analysis of existing data: Results of existing clinical studies will be analyzed to identify subgroups of patients with specific treatment responses and to identify systematic differences between the patient groups at the participating clinical centers. (2) Genetic and blood biomarker analysis: High throughput Whole Exome Sequencing (WES) will be performed in well-characterized chronic tinnitus cases, together with Proximity Extension Assays (PEA) for the identification of blood biomarkers for tinnitus. (3) RCT: A total of 500 patients will be recruited at five clinical centers across Europe comparing single treatments against combinational treatments. The four main treatments are Cognitive Behavioral Therapy (CBT), hearing aids, sound stimulation, and structured counseling. The consortium will also make use of e/m-health applications for the treatment and assessment of tinnitus. (4) Decision Support System: An innovative Decision Support System will be implemented, integrating all available parameters (epidemiological, clinical, audiometry, genetics, socioeconomic and medical history) to suggest specific examinations and the optimal intervention strategy based on the collected data. (5) Financial estimation analysis: A cost-effectiveness analysis for the respective interventions will be calculated to investigate the economic effects of the interventions based on quality-adjusted life years. In this paper, we will present the UNITI project, the scientific questions that it aims to address, the research consortium, and the organizational structure. © 2021 Elsevier B.V.

La elección de este caso se debe a la complejidad diagnóstica y terapéutica que ha supuesto y la escasa evolución positiva pese a los múltiples recursos humanos, profesionales, terapéuticos y farmacológicos invertidos. Se trata de un paciente con alteraciones de la conducta asociadas a un trastorno generalizado del desarrollo con sintomatología comórbida de TDAH, que posee un mundo imaginario que roza el pensamiento delirante. El paranoidismo, sin ninguna temporalidad en los hechos, le conduce a tener que vengarse en forma de pasos al acto violentos en el momento en que él cree ser la víctima. La evolución es tórpida, resaltando que esta mecánica de interpretación del mundo se presentaba generalmente como egosintónica, siendo muy escasas las ocasiones en que el paciente manifestaba, con llanto, un deseo de no querer hacer daño a nadie.

Summary Background Contaminated handwashing sinks have been identified as reservoirs that can facilitate colonization/infection of patients with multidrug-resistant (MDR) Gram-negative bacteria (GNB) in intensive care units (ICUs). Aim To assess the impact of removing patients' sinks and implementing other water-safe strategies on the annual rates of ICU-acquired MDR-GNB. Methods This six-year quasi-experimental study was conducted from January 2011 to December 2016. The intervention was carried out in August 2014 in two adult ICU wards with 12 rooms each. To assess the changes in annual MDR-GNB rates before and after the intervention, we used segmented regression analysis of an interrupted time-series. Crude relative risk (RR) rates were also calculated. Findings The incidence rates of MDR-GNB were 9.15 and 2.20 per 1000 patient-days in the pre- and post-intervention periods, respectively. This yielded a crude RR of acquiring MDR-GNB of 0.24 (95% confidence interval: 0.17–0.34). A significant change in level was observed between the MDR-GNB rate at the first point of the post-intervention period and the rate predicted by the pre-intervention time trend. Conclusion The implementation of a new water-safe policy, which included the removal of sinks from all patient rooms, successfully improved the control of MDR-GNB spread in an ICU with endemic infection. Our results support the contribution of sink use with the incidence of MDR-GNB in endemic environments.

Based on kinship terminologies collected for Batanic languages, this study reconstructs the Proto-Batanic kinship system and traces its transformations in present-day daughter communities. Since speakers of Batanic languages have maintained close contact among each other, the groups exhibit significant similarities not only in linguistic structure but also in certain cultural aspects such as kinship. All Batanic communities follow a lineal type of kinship(also known as Eskimo type), which is a retention of the ancestral Batanic kinship system. This is a departure from the generation type (also known as Hawaiian type) reconstructed for Proto-Philippines and Proto-Malayo-Polynesian. This development is analyzed as a reflection of changes in the behavior of the speakers, particularly in terms of rule of residence. Moreover,the physical house is seen as a reproduction of kinship relations in Batanic communities,where it serves as the primary locus of activities, rituals, and traditions that relate to kinship. Despite significant transformations in the kinship system of Batanic communities since their descent from Proto-Philippines, cultural features, particularly the value structure of Filipino communities, persist to this day.

Introduction Childhood acute leukemias (AL) and lymphomas achieve good survival rates. However, second neoplasms (SN) are a devastating event. Methods From August 1987 to December 2016, 34 of 3321 (1%) patients with diagnosis of AL or lymphoma developed SN. SN were AL (n=16), CNS tumors (n=5), endocrinal tumors (n=3), lymphomas (n=2), schwannoma (n=2) assorted sarcomas (n=4), retinal melanoma (n=1), and Vanek tumor (n=1). Median latency was 51 (range, 10 to 110) months for hematological malignancies and 119 (range, 25 to 236) months for solid tumors (P=0.001). Results A total of 33 patients with SN were treated taking into account cumulative doses of anthracyclines and radiotherapy. Twenty-three (67.6%) patients achieved complete remission (CR), 5 died early during therapy and 5 were refractory or partial responders. Six patients presented relapses of the SN and 1 died in CR. Seventeen patients remain alive in CR, with a median follow-up of 110 (range, 4 to 276) months. Conclusions (1) The latency period was significantly longer for patients developing solid tumors than for those developing AL. (2) AL was the most frequent SN. (3) Our results strongly encourage giving standard therapy to SN, considering cumulative doses of previous treatment, since similar probabilities of surviving as "de novo" counterparts can be achieved.

Nowadays, logistics can be described as an interdisciplinary strategy to optimize the production system. Availability is, therefore, the link between logistics and industrial maintenance. To manage this paradigm, maintenance management for a production process plays a key role. Therefore, the purpose of this paper is to design a holistic process-oriented approach to assess the impact of maintenance management on the distribution network and end-customer. As a result, impacts and interrelationships between maintenance and distribution towards the end-customers are derived. Based on the conceptual model, a simulation case study in a supply chain with a producer and its distribution network is developed. Goal is to observe the results of a certain maintenance strategy and its related maintenance characteristics in the subsequent steps of the production process and in the end-customer through the distribution network. The analysis of the case study is performed by means of simulation. The simulation model is built using System Dynamics (SD). Thanks to the scenarios and their results the impact of the maintenance strategy of one object could be observed. The impact depends also on other factors than only maintenance of the object such as customer demand, stocks, supply chain steps and proximity to end-customers.

The initiative created under the name “Industry 4.0” in 2011 [3] can help to strengthen the competitiveness of those manufacturing companies [4] able to adapt themselves to this fourth wave of technological advancement driven by various technological advances [5]. Most manufacturing companies have developed departments and initiated projects around the concept Industry 4.0. However, many of them lack the purpose, the organizational acceptance, and the alignment of those activities with the organization´s strategy. Therefore, the aim of this research is to design a conceptual model for improving organizational capabilities thanks to industry 4.0. For this development, the Viable System Model (VSM) was selected as methodological approach. The conceptual model determines the relations between technical areas, technologies, and organizational strategy. The model for Industry 4.0 can help manufacturing companies serving as a guidance for future organizational structure, projects, and activities selection as well as to determine areas with higher potentials according to the status of its technologies and their related current and future capabilities.

Management in companies today faces a true paradigm shift, characterized by a growing optimization of global value-added structures. To pursue this goal, lean philosophy is used as it allows applying sustainable improvements to the processes of a company, focusing on the value of the process and eliminating if possible or minimizing all those activities or tasks that when executed are not beneficial, that is, they do not add value. The research pursues to design and apply a systematic methodology to improve efficiency of a manufacturing plant increasing the value-added towards the end-customer. The objective of the work is to carry out an analysis of the manufacturing process of charged detonators to be potentially applied for other sectors. With the development of this work, it is described how it is possible to analyze, assess and implement improvement tools in manufacturing systems with a long tradition and that to date have not needed to improve their processes significantly due to market dynamics such as manufacturing of detonators. Moreover, a work methodology for optimizing manufacturing plants based on the proposed tools can be applied to other sectors.

Background We report results from the phase I dose-finding and phase II expansion part of a multicenter, open-label study of single-agent lenvatinib in pediatric and young adult patients with relapsed/refractory solid tumors, including osteosarcoma and radioiodine-refractory differentiated thyroid cancer (RR-DTC) (NCT02432274). Patients and methods The primary endpoint of phase I was to determine the recommended phase II dose (RP2D) of lenvatinib in children with relapsed/refractory solid malignant tumors. Phase II primary endpoints were progression-free survival rate at 4 months (PFS-4) for patients with relapsed/refractory osteosarcoma; and objective response rate/best overall response for patients with RR-DTC at the RP2D. Results In phase I, 23 patients (median age, 12 years) were enrolled. With lenvatinib 14 mg/m2, three dose-limiting toxicities (hypertension, n = 2; increased alanine aminotransferase, n = 1) were reported, establishing 14 mg/m2 as the RP2D. In phase II, 31 patients with osteosarcoma (median age, 15 years) and 1 patient with RR-DTC (age 17 years) were enrolled. For the osteosarcoma cohort, PFS-4 (binomial estimate) was 29.0% [95% confidence interval (CI) 14.2% to 48.0%; full analysis set: n = 31], PFS-4 by Kaplan–Meier estimate was 37.8% (95% CI 20.0% to 55.4%; full analysis set) and median PFS was 3.0 months (95% CI 1.8-5.4 months). The objective response rate was 6.7% (95% CI 0.8% to 22.1%). The patient with RR-DTC had a best overall response of partial response. Some 60.8% of patients in phase I and 22.6% of patients in phase II (with osteosarcoma) had treatment-related treatment-emergent adverse events of grade ≥3. Conclusions The lenvatinib RP2D was 14 mg/m2. Single-agent lenvatinib showed activity in osteosarcoma; however, the null hypothesis could not be rejected. The safety profile was consistent with previous tyrosine kinase inhibitor studies. Lenvatinib is currently being investigated in osteosarcoma in combination with chemotherapy as part of a randomized, controlled trial (NCT04154189), in pediatric solid tumors in combination with everolimus (NCT03245151), and as a single agent in a basket study with enrollment ongoing (NCT04447755)., Highlights • The recommended phase II dose of lenvatinib in children with relapsed/refractory solid malignant tumors is 14 mg/m2. • This dose is equivalent to the recommended dose of 24 mg/day for single-agent lenvatinib in adults with DTC. • Single-agent lenvatinib showed activity of interest in children and young adults with osteosarcoma. • Based on this initial report, lenvatinib is currently being investigated in combination with chemotherapy in osteosarcoma.

[EN] The effects of pressure on the crystal structure of aurophilic tetragonal gold iodide have been studied by means of powder X-ray diffraction up to 13.5 GPa. We found evidence of the onset of a phase transition at 1.5 GPa that is more significant from 3.8 GPa. The low- and high-pressure phases coexist up to 10.7 GPa. Beyond 10.7 GPa, an irreversible process of amorphization takes place. We determined the axial and bulk compressibility of the ambient-pressure tetragonal phase of gold iodide up to 3.3 GPa. This is extremely compressible with a bulk modulus of 18.1(8) GPa, being as soft as a rare gas, molecular solids, or organometallic compounds. Moreover, its response to pressure is anisotropic., The authors are thankful for the financial support of the Spanish Ministerio de Ciencia, Innovacion y Universidades, the Spanish Research Agency (AEI), and the European Fund for Regional Development (FEDER) under Grant MAT2016-75586-C4-1/2-P and of Generalitat Valenciana under Grant Prometeo/2018/123 (EFIMAT). J.A.S. acknowledges the "Ramon y Cajal" fellowship program (RYC-2015-17482) and Spanish Mineco Project FIS2017-83295-P. V.M. acknowledges the "Juan de la Cierva" program (FJCI-2016-27921) for financial support. Experiments were performed at the Materials Science and Powder Diffraction beamline of ALBA Synchrotron. The authors are thankful for the collaboration of ALBA staff and also thank D. Santamaria-Perez for fruitful discussions.

[EN] Raman scattering measurements have been performed in cadmium digallium sulphide (CdGa2S4) with defect chalcopyrite structure up to 25 GPa in order to study its pressure-induced phase transitions. These measurements have been complemented and compared with latticedynamics ab initio calculations including the TO-LO splitting at high pressures in order to provide a better assignment of experimental Raman modes. In addition, experimental and theoretical Gruneisen parameters have been reported in order to calculate the molar heat capacity and thermal expansion coefficient of CdGa2S4. Our measurements provide evidence that CdGa2S4 undergoes an irreversible phase transition above 15 GPa to a Raman-inactive phase, likely with a disordered rock salt structure. Moreover, the Raman spectrum observed on downstroke from 25 GPa to 2 GPa has been attributed to a new phase, tentatively identified as a disordered zinc blende structure, that undergoes a reversible phase transition to the Raman-inactive phase above 10 GPa. Published under license by AIP Publishing., The authors thank the financial support of the Spanish Ministerio de Economia y Competitividad (MINECO) under Grant Nos. MAT2016-75586-C4-2/3-P and MAT2015-71070-REDC (MALTA Consolider) and the Generalitat Valenciana under Project No. PROMETEO/2018/123-EFIMAT. E. P.-G., A. M., and P. R.-H. acknowledge computing time provided by Red Espanola de Supercomputacion (RES) and MALTA-Cluster.

Mutations in NPM1, FLT3 and CEBPA genes are found in 25-35 % of adult acute myeloblastic leukemia (AML) cases and correlate with prognosis. To date, there have been no reports about these mutations in pediatric AML from Argentina. The aims of the present study were to describe the incidence of NPM1, FLT3 and CEBPA mutations and to analyze their prognostic impact in this population. The incidences of these mutations within a population of 216 pediatric AML cases were: NPM1-mutated 4.2 %, CEBPA-mutated 1.9 %, FLT3-ITD 10.2 % and FLT3-TKD 7.9 %. Among 33 patients with normal karyotype, we found significantly higher frequencies for NPM1-mutated 24.2 % and CEBPA-mutated 12.1 %. Overall survival (pOS) for the 163 eligible non-acute promyelocytic leukemia cases was 46.2 ± 4.3 %, while leukemia-free survival probability was 51.0 ± 4.4 % (n = 135). The NPM1-mutated/FLT3-ITD-negative genotype showed better outcome than any other combined NPM1/FLT3 genotype; this difference was statistically significant within the group of high-risk patients (pOS ± SE 83.3 ± 15.2 % versus 33.1 ± 4.7 %; p = 0.0251). This is the first report of the frequencies of these mutations in Argentina. Despite the limited number of patients, a favorable prognosis of AML with genotype NPM1-mutated/FLT3-ITD-negative was confirmed. This is especially relevant within the high-risk group of patients, as it may contribute to the detection of patients with better prognosis, and thus avoid unnecessary treatment intensification.

Congenital gliobastoma multiforme (GBM) is rare and little is known about the molecular defects underlying the initiation and progression of this tumor type. We present a case of congenital GBM analyzed by conventional cytogenetics, fluorescence in situ hybridization, array comparative genomic hybridization and next generation sequencing. On cytogenetic analysis we detected a reciprocal translocation t(6;12)(q21;q24.3). By sequencing, the translocation was shown to form a fusion between the 5' region of ZCCHC8 and the 3' region of ROS1. RT-PCR analyses confirmed the existence of an in-frame fusion transcript with ZCCHC8 exons 1-3 joined to ROS1 exons 36-43. In addition to the ZCCHC8-ROS1 fusion, we detected a deletion in the short arm of chromosome 9, including homozygous loss of the CDKN2A/2B locus in 9p21.3 and heterozygous deletion of the HAUS6 gene in 9p22.1. The latter encodes a protein involved in faithful chromosome segregation by regulating microtubule nucleation and its deletion might be associated with the marked subclonal changes of ploidy observed in the tumor. This report adds the ZCCHC8-ROS1 fusion as oncogenic driver in GBM and supports the role of ROS1 activation in the pathogenesis of a subset of GBM. © 2016 Wiley Periodicals, Inc.

The association between mature-B phenotype and MLL abnormalities in acute lymphoblastic leukemia (ALL) is a very unusual finding; only 14 pediatric cases have been reported so far. We describe the clinical and biological characteristics and outcome of five pediatric cases of newly diagnosed B lineage ALL with MLL abnormalities and mature immunophenotype based on light chain restriction and surface Ig expression. Blasts showed variable expression of CD10/CD34/TdT. MLL abnormalities with no MYC involvement were detected in all patients by G-banding, FISH, and/or RT-PCR. Three patients were treated according to Interfant protocol, one to ALLIC-09, and one received B-NHL-BFM-2004. All patients achieved complete remission and three of them relapsed. Despite the small cohort size, it could be postulated that B lineage ALL with MLL abnormalities and mature phenotype is a distinct entity that differs both from the typical Pro B ALL observed in infants and mature B-ALL with high MYC expression.

Saccharomyces pastorianus lager brewing yeasts are domesticated hybrids of Saccharomyces cerevisiae and cold-tolerant Saccharomyces eubayanus. To understand the contribution of both parental genomes to maltose metabolism in brewing wort, this study focuses on maltose transport in the S. eubayanus type strain CBS 12357T/FM1318. To obtain complete sequences of the MAL loci of this strain, a near-complete genome assembly was generated using the Oxford Nanopore Technology MinION sequencing platform. Except for CHRXII, all sixteen chromosomes were assembled as single contigs. Four loci harboring putative maltose transporter genes (SeMALT1-4), located in subtelomeric regions of CHRII, CHRV, CHRXIII, and CHRXVI, were completely resolved. The near-identical loci on CHRV and CHRXVI strongly resembled canonical S. cerevisiae MAL loci, while those on CHRII and CHRXIII showed different structures suggestive of gene loss. Overexpression of SeMALT1-4 in a maltose-transport-deficient S. cerevisiae strain restored growth on maltose, but not on maltotriose, indicating maltose-specific transport functionality of all four transporters. Simultaneous CRISPR-Cas9-assisted deletion of only SeMALT2 and SeMALT4, which shared 99.7% sequence identity, eliminated growth of S. eubayanus CBS 12357T on maltose. Transcriptome analysis of S. eubayanus CBS 12357T established that SeMALT1 and SeMALT3, are poorly expressed in maltose-grown cultures, while SeMALT2 and SeMALT4 were expressed at much higher levels than SeMALT1 and SeMALT3, indicating that only SeMALT2/4 are responsible for maltose consumption in CBS 12357T. These results represent a first genomic and physiological characterization of maltose transport in S. eubayanus CBS 12357T and provides a valuable resource for further industrial exploitation of this yeast.