The underlying social dynamics of paradigm shifts

We develop here a multi-agent model of the creation of knowledge (scientific progress or technological evolution) within a community of researchers devoted to such endeavors. In the proposed model, agents learn in a physical-technological landscape, and weight is attached to both individual search and social influence. We find that the combination of these two forces together with random experimentation can account for both i) marginal change, that is, periods of normal science or refinements on the performance of a given technology (and in which the community stays in the neighborhood of the current paradigm); and ii) radical change, which takes the form of scientific paradigm shifts (or discontinuities in the structure of performance of a technology) that is observed as a swift migration of the knowledge community towards the new and superior paradigm. The efficiency of the search process is heavily dependent on the weight that agents posit on social influence. The occurrence of a paradigm shift becomes more likely when each member of the community attaches a small but positive weight to the experience of his/her peers. For this parameter region, nevertheless, a conservative force is exerted by the representatives of the current paradigm. However, social influence is not strong enough to seriously hamper individual discovery, and can act so as to empower successful individual pioneers who have conquered the new and superior paradigm.Fil: Rodriguez Sickert, Carlos. Universidad del Desarrollo; ChileFil: Cosmelli, Diego. Pontificia Universidad Católica de Chile; ChileFil: Claro, Francisco. Pontificia Universidad Católica de Chile; ChileFil: Fuentes, Miguel Angel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad San Sebastián; Chil

Vasotocin and isotocin regulate aquaporin 1 function in the sea bream

Aquaporins (AQPs) are specific transmembrane water channels with an important function in water homeostasis. In terrestrial vertebrates, AQP2 function is regulated by vasopressin (AVP) to accomplish key functions in osmoregulation. The endocrine control of aquaporin function in teleosts remains little studied. Therefore, in this study we investigated the regulatory role of vasotocin (AVTR) and isotocin (ITR) receptors in Aqp1 paralog gene function in the teleost gilthead sea bream (Sparus aurata). The complete coding regions of Aqp1a, Aqp1b, AVTR V1a2-type, AVTR V2-type and ITR from sea bream were isolated. A Xenopus oocyte-swelling assay was used to functionally characterize AQP1 function and regulation by AVT and IT through their cognate receptors. Microinjection of oocytes with Aqp1b mRNA revealed regulation of water transport via PKA (IBMX+forskolin sensitive), whereas Aqp1a mRNA injection had the same effect via PKC signaling (PDBU sensitive). In the absence of expressed receptors, AVT and IT (10(-8) mol l(-1)) were unable to modify AQP1 function. AVT regulated AQP1a and AQP1b function only when the AVTR V2-type was co-expressed. IT regulated AQP1a function, but not AQP1b, only when ITR was present. Considering that Aqp1a and Aqp1b gene expression in the sea bream intestine is highly salinity dependent in vivo, our results in ovo demonstrate a regulatory role for AVT and IT in AQP1 function in the sea bream in the processing of intestinal fluid to achieve osmoregulation.Ministry of Education (Spain) [FPU AP2008-01194]; Portuguese National Science Foundation [SFRH/BPD/66808/2009]; Ministry of Science and Education, Spain [AGL2010-14876]; National Science Foundation (FCT, Portugal) [PTDC/MAR-BIO/3811/2012

EMOTIONAL PERCEPTION AND CULTURAL MOTIVATION ON LOYALTY TO A WORLD HERITAGE SITES DESTINATION

The aim of this paper is to contribute to the scientific literature in the field of tourism in Latin America (Sucre, Bolivia was named a World Heritage Site (WHS) by UNESCO). This study analyses the relevance of the cultural motivation and emotional experience of the tourist to positively influence the image or the perceived value of the heritage site visited. The research shall also analyse other relationships, such as the positive effect of the perceived value on the loyalty of tourists and the influence of the visitor’s place of origin as a moderating variable in the formation of the image and loyalty to the destination. The analysis was performed by means of structural equation models (SEMs). The data were extracted through fieldwork consisting of interviews with visitors to the city. The results of the research revealed that the perceived value of a heritage destination not only depends on the functional and tangible aspects of the attributes but also on the emotional experience and cultural interest regarding the heritage site visited. Similarly, there is evidence of a relationship between perceived value and a loyal attitude and that it is moderated by the origin of the tourist, this being a great influence in the case of the domestic tourist

Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines

We have determined the effects of the IGF-1R tyrosine kinase inhibitors BMS-754807 (BMS) and OSI-906 (OSI) on cell proliferation and cell-cycle phase distribution in human colon, pancreatic carcinoma, and glioblastoma cell lines and primary cultures. IGF-1R signaling was blocked by BMS and OSI at equivalent doses, although both inhibitors exhibited differential antiproliferative effects. In all pancreatic carcinoma cell lines tested, BMS exerted a strong antiproliferative effect, whereas OSI had a minimal effect. Similar results were obtained on glioblastoma primary cultures, where HGUE-GB-15, -16 and -17 displayed resistance to OSI effects, whereas they were inhibited in their proliferation by BMS. Differential effects of BMS and OSI were also observed in colon carcinoma cell lines. Both inhibitors also showed different effects on cell cycle phase distribution, BMS induced G2/M arrest followed by cell death, while OSI induced G1 arrest with no cell death. Both inhibitors also showed different effects on other protein kinases activities. Taken together, our results are indicative that BMS mainly acts through off-target effects exerted on other protein kinases. Given that BMS exhibits a potent antiproliferative effect, we believe that this compound could be useful for the treatment of different types of tumors independently of their IGF-1R activation status.This research was funded by a Grant from Instituto de Salud Carlos III Grant PI012/02025 co-supported by FEDER funds and PRECIPITA crowdfunding platform from Fundación Española para la Ciencia y la Tecnología (Fecyt) to M. Saceda and AMACMED (Asociación de mujeres afectadas por cáncer de mama de Elche y Comarca) and Monica Moraleda donation to M. Saceda. The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21) and the Generalitat Valenciana (PROMETEO/2016/006) supported the work in the Encinar laboratory

Microvascular cutaneous coverage in wounds that expose the Achilles tendon: case report

Achilles tendon rupture, being one of the main tendon ruptures present, surgery being the most favourable option even taking into account complications such as infections and skin necrosis, it is necessary to develop techniques which help to reduce complications and increase benefits. The methods follow-up of 2 cases of patients with skin defects in the region of the Achilles tendon in patients who were treated at the "Luis Guillermo lbarra lbarra" national rehabilitation institute during the period 2020-2021 in the Traumatology service, treated with radial free flap forearm, using the description of the most used flaps in the literature. Results in both cases integrity of the free radial forearm flap in its entirety, functional recovery for walking, ability to put shoes back on, and without the need for reoperation, as well as a high level of satisfaction by patients. Conclusions if we are talking about an Achilles tendon rupture with a significant skin defect, the free radial forearm flap is an adequate option, if we are talking about a complete defect, the composite flap is the best option, remember that the decision on what type of flap will be used will depend on of the size of the lesion

A method of localizing the spectra of sequences of orthogonal polynomials

AbstractOne of the trends in the theory of orthogonal polynomials is to get as much information on their behaviour as possible from the recurrence relation they satisfy. Our intention is to propose a method which in any particular case allows to localize the spectra of polynomial sequences orthogonal either on the real line or on the complex plane

Microbiota diversity in nonalcoholic fatty liver disease and in drug-induced liver injury

The gut microbiota could play a significant role in the progression of nonalcoholic fatty liver disease (NAFLD); however, its relevance in drug-induced liver injury (DILI) remains unexplored. Since the two hepatic disorders may share damage pathways, we analysed the metagenomic profile of the gut microbiota in NAFLD, with or without significant liver fibrosis, and in DILI, and we identified the main associated bacterial metabolic pathways. In the NAFLD group, we found a decrease in Alistipes, Barnesiella, Eisenbergiella, Flavonifractor, Fusicatenibacter, Gemminger, Intestinimonas, Oscillibacter, Parasutterella, Saccharoferementans and Subdoligranulum abundances compared with those in both the DILI and control groups. Additionally, we detected an increase in Enterobacter, Klebsiella, Sarcina and Turicibacter abundances in NAFLD, with significant liver fibrosis, compared with those in NAFLD with no/mild liver fibrosis. The DILI group exhibited a lower microbial bacterial richness than the control group, and lower abundances of Acetobacteroides, Blautia, Caloramator, Coprococcus, Flavobacterium, Lachnospira, Natronincola, Oscillospira, Pseudobutyrivibrio, Shuttleworthia, Themicanus and Turicibacter compared with those in the NAFLD and control groups. We found seven bacterial metabolic pathways that were impaired only in DILI, most of which were associated with metabolic biosynthesis. In the NAFLD group, most of the differences in the bacterial metabolic pathways found in relation to those in the DILI and control groups were related to fatty acid and lipid biosynthesis. In conclusion, we identified a distinct bacterial profile with specific bacterial metabolic pathways for each type of liver disorder studied. These differences can provide further insight into the physiopathology and development of NAFLD and DILI.This work was supported in part by a grant from the Instituto de Salud Carlos III (Spain) (PI18/01804, PI19/00883, PI21/01248), from the Consejería de Economía, Conocimiento, Empresas y Universidad (Junta de Andalucía, Spain) (PI18–RT‐3364, UMA18-FEDERJA-194), and from the Consejería de Salud (Junta de Andalucía, Spain) (PI-0285–2016). This study has been co-funded by FEDER funds (“A way to make Europe”) (“Andalucía se mueve con Europa”). CRD is supported by a grant from the Consejería de Transformación Económica, Industria, Conocimiento y Universidades de Junta de Andalucía (Spain) (DOC_01610). FMR is supported by a grant from the ISCIII (Spain) (FI19/00189). AC is supported by a grant from the ISCIII (Spain) (IFI18/00047). EGF is supported by the Nicolas Monardes program from the Consejería de Salud de Andalucía (Spain) (C-0031–2016). Funding for open access charge: Universidad de Málaga / CBUA (Spain)

Adjuvant dabrafenib and trametinib for patients with resected BRAF-mutated melanoma: DESCRIBE-AD real-world retrospective observational study

BRAF and MEK inhibitor, dabrafenib plus trametinib, adjuvant therapy is effective for high-risk resected melanoma patients with BRAF-V600 mutations. However, real-world evidence is limited. We aimed to determine the feasibility of this therapy in routine clinical practice. DESCRIBE-AD, a retrospective observational study, collected real-world data from 25 hospitals in Spain. Histologically confirmed and resected BRAF-mutated melanoma patients aged & GE;18 years who were previously treated with dabrafenib plus trametinib adjuvant therapy, were included. The primary objectives were treatment discontinuation rate and time to discontinuation. The secondary objectives included safety and efficacy. From October 2020 to March 2021, 65 patients were included. Dabrafenib and trametinib discontinuation rate due to treatment-related adverse events (TRAEs) of any grade was 9%. Other reasons for discontinuation included patients' decisions (6%), physician decisions (6%), unrelated adverse events (3%), disease progression (5%), and others (5%). The median time to treatment discontinuation was 9 months [95% confidence interval (CI), 5-11]. G3-4 TRAEs occurred in 21.5% of patients, the most common being pyrexia (3%), asthenia (3%), and diarrhoea (3%). Unscheduled hospitalisations and clinical tests occurred in 6 and 22% of patients, respectively. After 20-month median follow-up (95% CI, 18-22), 9% of patients had exitus due to disease progression, with a 12-month relapse-free survival and overall survival rates of 95.3% and 100%, respectively. Dabrafenib and trametinib adjuvant therapy proved effective for melanoma patients in a real-world setting, with a manageable toxicity profile. Toxicity frequencies were low leading to low incidence of unscheduled medical visits, tests, and treatment discontinuations

Incidence of and factors associated with SARS-CoV-2 infection among people living with HIV in Southern Spain after one year of pandemic

Whether people living with HIV (PLWH) are at greater risk of acquiring SARS-CoV-2 infection is currently unknown. Prospective serologic studies may allow seroincidence analyses, where all infections are accurately identified. Because of this, we evaluated the incidence of associated factors with and the clinical outcome of SARS-CoV-2 infection in PLWH in Southern Spain. This prospective cohort study included PLWH from a Tertiary University Hospital in Southern Spain. Patients were enrolled in the study if (1) they had attended as outpatients our Unit from 1 August 2019 to 8 February 2020 and (2) had two subsequent evaluations from 9 February 2020 to 4 March 2021. SARS-CoV-2 infections were diagnosed by PCR, antigen detection or serology. Seven hundred and nine PLWH were included in the study. Of them, 55 [7.8%, 95% confidence interval (95% CI) 5.9%-9.9%] patients developed SARS-CoV-2 infection. Between 18 May and 29 November 2020, the rate of seroconversion was 5.3% (95% CI: 3.1%-9.0%) for the general population in the area of Seville and 2.3% (95% CI: 1.3%-2.6%) for PLWH in this study (p = .001). After multivariable analysis, adjusted by age, sex, and risk factors for HIV infection, active tobacco use and CDC stage, active tobacco smoking was the only factor independently associated with lower risk of SARS-Cov-2 infection [Incidence rate ratio: 0.29 (95% CI 0.16-0.55) p < .001]. In conclusion, the incidence of SARS-CoV-2 infection among PLWH in Southern Spain during the ongoing pandemic was lower than that reported for the general population in the same area.This work was supported in part by the Instituto de Salud CarlosIII (Project ‘PI16/01443’), integrated in the national I+D+i 2013–2016andco-fundedbytheEuropeanUnion(ERDF/ESF,‘Investinginyour future’), by the Spanish Network for AIDS investigation (RIS)(www.red.es/redes/inicio)(RD16/0025/0010,RD16/0025/0040),asapartoftheNacionalI+D+I,ISCIIISubdirecciónGeneraldeEvaluaciónand the European Fund for Development of Regions (FEDER). JuanA.PinedareceivedaresearchextensiongrantfromtheProgramadeIntensificacióndelaActividaddeInvestigacióndelServicioNacionaldeSaludCarlosIII(I3SNS).FedericoGarciareceivedaresearchextensiongrantfromtheProgramadeIntensificacióndelaActividaddeInves-tigacióndelServicioAndaluzdeSalud.AnaïsCorma-GomezreceivedaRíoHortegagrantfromtheInstitutodeSaludCarlosIII(grantnum-ber CM19/00251). Funding for open access charge: Universidad deMálaga/CBU