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Effectiveness and safety of first-generation protease inhibitors in clinical practice:Hepatitis C virus patients with advanced fibrosis

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World Journal of Gastroenterology 2015年第30期21卷 9163-9174页

作者： javier Salmeron Carmen Vinaixa Ruben Berenguer Juan Manuel Pascasio Juan Jose Sanchez Ruano Miguel angel Serra Ana Gila Moises Diago Manuel Romero-Gomez Jose Maria Navarro Milagros Testillano Conrado Fernandez Dolores Espinosa Isabel Carmona Jose Antonio Pons francisco Jorquera francisco javier rodriguez Ramon Perez Jose Luis Montero Rafael Granados Miguel Fernandez Ana Belen Martin Paloma Munoz de Rueda Rosa Quiles CIBERehd Instituto de Salud Carlos Ⅲ28029 MadridSpain Unit for Clinical Management of Digestive Diseases Complejo Hospitalario Universitario de Granada Instituto de Investigacion Biosanitaria de Granada University Hospital Politecnico La Fe Unit for Clinical Management of Digestive Diseases University Hospital Virgen Del Rocio Hospital Toledo University Clinic Hospital of Valencia University General Hospital of Valencia Unit for Clinical Management of Digestive Diseases University Hospital Nuestra Senora de Valme Department of Gastroenterology and Hepatology Agencia Sanitaria Costa del Sol University Hospital Cruces Gastroenterology Unit University Hospital Fundacion Alcorcon University Hospital Virgen Macarena University Hospital Virgen de la Arrixaca Hospital of Leon University General Hospital Reina Sofia Department Gastroenterology and Hepatology University Hospital Central de Asturias University Hospital Reina Sofia University Hospital De Gran Canaria Dr. Negrin Hospital San Pedro de Alcantara

AIM:To evaluates the effectiveness and safety of the first generation,NS3/4A protease inhibitors(PIs) in clinical practice against chronic C virus,especially in patients with advanced fibrosis. METHODS:Prospective study and non-experimental analysis of a multicentre cohort of 38 Spanish hospitals that includes patients with chronic hepatitis C genotype 1,treatment-na?ve(TN) or treatment-experienced(TE),who underwent triple therapy with the first generation NS3/4A protease inhibitors,boceprevir(BOC) and telaprevir(TVR),in combination with pegylated interferon and ribavirin. The patients were treatment in routine practice settings. Data on the study population and on adverse clinical and virologic effects were compiled during the treatment period and during follow ***:One thousand and fifty seven patients were included,405(38%) were treated with BOC and 652(62%) with TVR. Of this total,30%(n = 319) were TN and the remaining were TE:28%(n = 298) relapsers,12%(n = 123) partial responders(PR),25%(n = 260) null-responders(NR) and for 5%(n = 57) with prior response unknown. The rate of sustained virologic response(SVR) by intention-to-treatment(ITT) was greater in those treated with TVR(65%) than in those treated with BOC(52%)(P < 0.0001),whereas by modified intention-to-treatment(m ITT) no were found significant differences. By degree of fibrosis,56% of patients were F4 and the highest SVR rates were recorded in the non-F4 patients,both TN and TE. In the analysis by groups,the TN patients treated with TVR by ITT showed a higher SVR(P = 0.005). However,by m ITT there were no significant differences between BOC and TVR. In the multivariate analysis by m ITT,the significant SVR factors were relapsers,IL28 B CC and non-F4; the type of treatment(BOC or TVR) was not significant. The lowest SVR values were presented by the F4-NR patients,treated with BOC(46%) or with TVR(45%). 28% of the patients interrupted the treatment,mainly by non-viral response(51%):this outcome was

关键词： Hepatitis C Boceprevir Telaprevir First-generation protease inhibitors Advanced fibrosis

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Generating native user interfaces for multiple devices by means of model transformation

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Frontiers of Information Technology & Electronic Engineering 2015年第12期16卷 995-1017页

作者： Ignacio MARIN francisco ORTIN German PEDROSA javier rodriguez Department of Research and Development CTIC Foundation Department of Computer Science University of Oviedo

In the last years, the types of devices used to access information systems have notably increased using different operating systems, screen sizes, interaction mechanisms, and software features. This device fragmentation is an important issue to tackle when developing native mobile service front-end applications. To address this issue,we propose the generation of native user interfaces(UIs) by means of model transformations, following the modelbased user interface(MBUI) paradigm. The resulting MBUI framework, called LIZARD, generates applications for multiple target platforms. LIZARD allows the definition of applications at a high level of abstraction, and applies model transformations to generate the target native UI considering the specific features of target platforms. The generated applications follow the UI design guidelines and the architectural and design patterns specified by the corresponding operating system manufacturer. The objective is not to generate generic applications following the lowest-common-denominator approach, but to follow the particular guidelines specified for each target device. We present an example application modeled in LIZARD, generating different UIs for Windows Phone and two types of Android devices(smartphones and tablets).

关键词： Model-to-model transformation Native user interfaces Model-based user interfaces Model-driven engineering

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Validation of GIS layers in the EU:getting adapted to available reference data

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International Journal of Digital Earth 2011年第S1期4卷 42-57页

作者： francisco javier Gallego IPSC Joint Research Centre of the ECIspraItaly

An optimal validation of a thematic map would ideally require in-situ observations of a large sample of units specifically conceived for the map under *** is often not possible due to budget *** alternative can be using photo-interpretation of high or very high resolution images instead of in-situ observations or using available data sets that do not fully comply with the ideal characteristics:unit size,reference date or sampling *** paper illustrates some examples of use of available data in the European *** land cover maps,the best existing data set is probably Land Use/Cover Areaframe Survey(LUCAS)that has been conducted by Eurostat on four occasions since *** LUCAS is based on systematic sampling,advantages and limitations of systematic sampling are discussed.A fine-scale population density map is presented as an example of a situation in which reference data on a statistical sample cannot be collected.

关键词： accuracy assessment area frame sampling systematic sampling LUCAS land cover maps population density

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Powder metallurgy with space holder for porous titanium implants:A review

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Journal of Materials Science & Technology 2021年第17期76卷 129-149页

作者： Alejandra rodriguez-Contreras Miquel Punset JoséA.Calero francisco javier Gil Elisa Ruperez JoséMaría Manero Biomaterials Biomechanics and Tissue Engineering Group(BBT)Department of Materials Science and EngineeringUniversitat Politecnica de Catalunya(UPC)Av.Edurad Maristany 1608019BarcelonaSpain Barcelona Research Centre in Multiscale Science and Engineering Technical University of Catalonia(UPC)Av.Eduard Maristany 10-1408019BarcelonaSpain UPC Innovation and Technology Center(CIT-UPC).Technical University of Catalonia(UPC) C.Jordi Girona 3-108034Barcelona.Spain AMES GROUP SA.Carretera Nacional 340 Pol.Ind."Les Fallulles"08620Sant Vicenc dels HortsBarcelonaSpain Bioengineering Institute for Technology Universitat Intemacional de Catalunyac/Josep Trueta s/n08195BarcelonaSpain

One of the biggest challenges in the biocompatibility of implantable metals is the prevention of the stress shielding effect,which is related to the coupling of the bone-metal mechanical *** stress shielding phenomenon provokes bone resorption and the consequent adverse effects on prosthesis ***,it can be inhibited by adapting the stiffness of the implant *** the use of titanium(Ti)porous structures is a great alternative not only to inhibit this effect but also to improve the osteointegration of orthopedic and dental implants,a brief description of the techniques used for their manufacturing and a review of the current commercialized implants produced from porous Ti assemblies are compiled in this *** powder metallurgy(PM)with space holder(SH)is a powerful technology used to produce porous Ti structures,it is here discussed its potential for the fabrication of medical devices from the perspectives of both design and *** most important parameters of the technique such as the size and shape of the initial metallic particles,the SH and binder type of materials,the compaction pressure of the green form,and in the sintering stage,the temperature,atmosphere,and time are reviewed according to the bibliography ***,the importance of the porosity and its types together with the influence of the mentioned parameters in the final porosity and,consequently,in the ultimate mechanical properties of the structure are ***,a few examples of the PM-SH application for the manufacturing of orthopedic implants are presented.

关键词： Powder metallurgy Space holder method Porous titanium structures Medical devices Stress shielding effect Porous materials permeability Interconnected porosity Porous bone substitute materials Open-cell titanium foams Sintering-dissolution technique

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Pathogenesis of glaucoma: how to prevent ganglion cell from axonal destruction?

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Neural Regeneration Research 2014年第23期9卷 2046-2047页

作者： francisco javier Carreras Department of Surgery(Ophthalmology) Faculty of MedicineUniversity of Granada

Glaucoma is the main cause of irreversible blindness globally, but the pathogenesis of glaucoma is still pending consensus. In spite of great advances during the 20th and early 21st centuries in terms of detailed knowledge of pathological processes that take place in glaucoma, the exact pathogenesis is much less clear. Hypotheses abound, and the most researched areas are ischemia at the optic nerve head, blockade of ganglion cell axonal transport, peripapillary atrophy, and changes in the characteristics of the lamina cribrosa （Nucci et al., 2008）.

关键词： Pathogenesis of glaucoma RGCs cell

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Lessons from glaucoma: rethinking the fluid-brain barriers in common neurodegenerative disorders

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Neural Regeneration Research 2019年第6期14卷 962-966页

作者： francisco javier Carreras Department of Surgery Faculty of MedicineUniversity of Granada

Glaucoma has been recently characterized as a member of the group of anoikis-related diseases. Anoikis, a form of apoptosis, can be triggered by the unfastening of adherent junctions present in astrocytes. In those areas of the central nervous system in which the soma of the neurons or their axons and dendrites are metabolically dependent on the activity of astrocytes, a derangement of the lactate shuttle caused by a separation between the plasma membranes of neurons and astrocytes would result in metabolic impairment of the neurons themselves. In glaucoma, the triggering event has been attributed to the posterior deviation of aqueous humor towards the astrocyte-rich prelaminar tissue of the optic nerve head. The mean calcium content in the aqueous is able to interfere with calcium-dependent adherent junctions and induce anoikis of the astrocytes. As the cerebrospinal fluid has a similar base calcium concentration, a shunt of cerebrospinal fluid through the cerebral parenchyma would be able to interfere in the astrocytic architecture with dire consequences to the metabolically dependent neurons. Here the similitude between glaucoma,amyotrophic lateral sclerosis and Alzheimer's disease are discussed and the concept of the break in the fluid-brain barrier, as an event separated from the blood-brain barrier, is stressed.

关键词： fluid-brain barriers blood-brain barrier cerebrospinal fluid aqueous humor calcium ion glaucoma amyotrophic lateral sclerosis Alzheimer’s disease

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Sex and habitat differences in size and coloration of an amphibian’s poison glands match differential predator pressures

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Integrative Zoology 2022年第5期17卷 764-776页

作者： francisco javier ZAMORA-CAMACHO Department of Phisical Chemical and Natural SystemsPablo de Olavide UniversitySevilleSpain Department of Biodiversity Ecology and EvolutionComplutense University of MadridMadridSpain

Chemical defenses are frequently accompanied by salient color patterns actively avoided by predators,a phe-nomenon referred to as ***,the production of both chemical defenses and pigments is costly,and is thus expected to be reduced under mild predator *** this work,I compared the size and coloration of parotoid glands(2 dorsal,external swollen structures that secrete toxins in toads)of male and female Epidalea calamita toads from agrosystems and from pine groves.I also quantiﬁed the predator attacks received by plas-ticine toad models,whose“parotoid glands”differed in size and color conspicuousness,exposed in each *** avoided models with large and conspicuous parotoid glands,but models in agrosystems were more of-ten *** actual toads,agrosystem and male individuals had larger parotoid glands,presumably implying greater production of chemical defenses than in pine grove and female conspeciﬁ***ﬁndings are aligned with previous research suggesting that both agrosystem toads and males in this system are subjected to a more intense predator *** between parotoid gland and dorsum coloration was greater in agrosys-tem toads.A marked internal pattern could function as an aposematic signal,which could counteract increased predator pressure.

关键词： anuran agrosystem aposematism Epidalea calamita plasticine model

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Integrating time progression in ecoimmunology studies: beyond immune response intensity

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Current Zoology 2019年第2期65卷 205-212页

作者： francisco javier ZAMORA-CAMACHO Department of Biological Sciences Dartmouth College Hanover New Hampshire USA Department of Biogeography and Global Change Museo Nacional de Ciencias Naturales (MNCN) Spanish National Research Council (CSIC) Madrid Spain

Habitat alterations in agroecosystems may damage amphibian immune capacity. As agroecosystem extension is increasing worldwide, broader-context knowledge on the effects of agroecosystem stressful conditions on amphibian immune capacity is crucial for understanding and management of amphibian global declines. However, most studies on ecoimmunology assume synchronal amonggroup immune-response peaks, and focus on immune response after standardized time lapses, neglecting its progress!on. Herein, I compared inflamatory response short-term progression of agro ecosystem and n atural-habitat female and male n atterjack toads Epi da lea calamita, by measuri ng swelling response, once per hour, 6 h following an artificial immune challenge with innocuous antigen phytohemagglutinin. I also compared maximum magnitude of swelling response, irrespective of the moment when it was reached. Habitat differences arose only 3 h after challenge, when naturalhabitat toads showed greater swelling response. Maximum magnitude of swelling response was similar in toads from both habitats. However, agroecosystem toads showed a delayed swelling response as compared with natural-habitat conspecifics, probably as a consequenee of agroecosystem stressful conditions. Such a delay suggests a weaker immune capacity, and consequently impaired anti-pathogen performance. Regarding sex, swelling response magnitude did not differ between males and females. Female swelling response peaked earlier, but that of males was more sustai ned in time, which con tradicts general across-taxa fin dings that males show impaired immune response. Interestingly, results suggest that measuring swelling response only after some standardized period following stimulation may be a simplistic approach and produce unrealistic results. Consequently, studies on ecoimmunology should implement swelling response progression in order to produce unbiased science.

关键词： agroecosystem amphibian immunocompetence natural habitat immune response progressi on

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Glaucoma and amyotrophic lateral sclerosis,two kindred diseases?

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Neural Regeneration Research 2016年第9期11卷 1415-1417页

作者： francisco javier Carreras Surgery Department Faculty of MedicineUniversity of Granada

Amyotrophic lateral sclerosis （ALS）, a predominantly sporadic disease with unknown etiology and pathogeny, is a member of a group known as motor neuron diseases （MND）. The heterogeneity of the clinical presentation of the disease is a fundamental aspect of ALS and is de- termined by the variable engagement of its upper motor neuron （UMN） and lower motor neuron （LMN） components （Ravits and La Spada, 2009）.

关键词： RGCs Glaucoma and amyotrophic lateral sclerosis,two kindred diseases Figure

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Diffusion dynamics and characterization of attogram masses in optically trapped single nanoparticles using laser-induced plasma imaging

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Nano Research 2023年第5期16卷 7470-7480页

作者： Pablo Purohit francisco J.Fortes javier Laserna UMALASERLAB Departamento de Química AnalíticaUniversidad de MálagaC/Jiménez Fraud 4Malaga 29010Spain Niels Bohr Institute University of CopenhagenBlegdamsvej 172100 CopenhagenDenmark

In the present work,a wavelength-selected plasma imaging analysis system is presented and used to track photons emitted from single-trapped nanoparticles in air at atmospheric *** isolated nanoentities were atomized and excited into plasma state using single nanosecond laser *** use of appropriate wavelength filters alongside time-optimized acquisition settings enabled the detection of molecular and atomic emissions in the *** photon detection efficiency of the imaging line resulted in a signal>400 times larger than the simultaneously-acquired dispersive spectroscopy *** increase in sensitivity outlined the evolution of diverse physicochemical processes at the single particle scale which included heat and momentum transfer from the plasma into the particle as wells as chemical *** imaging detection of excited fragments evidenced different diffusion kinetics and time frames for atoms and molecules and their influence upon both the spectroscopic emission readout and fabrication processes using the plasma as a ***,the origin of molecular species,whether naturally-occurring or derived from a chemical reaction in the plasma,could also be studied on the basis of compositional gradients found on the *** of detection for the inspected species ranged from tens to hundreds attograms,thus leading to an exceptional sensing principle for single nanoentities that may impact several areas of science and technology.

关键词： single nanoparticle inspection wavelength-selected laser-induced plasma imaging laser fabrication attogram characterization atomic/molecular diffusion

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