ELF Pedagogy in Spain and the UK

Our research project shows that exposing ELT practitioners to language change and to reflective attitudes towards language and towards new developments in ELT methodology can in return help them envisage an ELF aware pedagogical approach. Our research project has three phases: a) understanding pre-service ELT practitioners’ attitudes towards ELF and ELF Pedagogy; b) analyzing in-service ELT practitioners’ attitudes towards ELF and ELF Pedagogy; c) Observing and assessing classroom implementations of ELF-aware strategies. We are currently conducting the second stage. Educational context, teachers’ experience, and field of expertise affect the level of understanding and commitment to ELF Pedagogy. A comparison between both institutions will be presented together with data addressing the differences between the first and the second stages of the project.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

English as a lingua franca in higher education: local perspectives of a global phenomenon. The case study of the University of Málaga

English as a Lingua Franca in higher education: Local perspectives of a global phenomenon. The case study of the University of Málaga PINEDA, INMACULADA (Universidad de Málaga) This presentation introduces the main themes of the round table, arguing that challenging teachers’ and language policymakers’ perceptions of language use can be a way to expose them to English as a Lingua Franca (ELF henceforth) ideas and its implications for an ELF-aware teaching approach. The focus of the round table is to understand how ELF is studied, perceived and applied locally in the context of five Spanish universities. The data presented regarding the University of Málaga will describe the efforts that have been made to increase ELF awareness among English as a Medium of Instruction (EMI henceforth) professors actively teaching at a number of degrees (Architecture, Criminology, Fine Arts, Gynecology). As part of a global trend, the number of EMI courses offered at the University of Málaga, encompassing a majority of Nonnative English speakers (NNESs henceforth) with different L1s along with some Native English Speakers (NESs henceforth), has greatly increased in the last decade: 300% more for the Architecture degree; 200% more for Criminology and also for Fine Arts; and a prediction of 6 new EMI courses for the degree in Medicine. The different phases of implementation of our teacher training programs will be discussed and their concurrence with other NES-centered courses. The complexity of views about ELF and the multiple types of implementation of an ELF-aware approach will also be described. The contribution will end both by establishing a number of common features among the different papers included in this round table and by formulating a number of questions regarding ELF awareness, ELF use and ELF research that will hopefully encourage audience participation.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Time course of transcription and chromatin states during batch culture in Chinese Hamster ovary cells

Chinese Hamster Ovary (CHO) cells are known to be easily adapted to different culture conditions and to be highly variable. Beside genetic alterations, epigenetic regulation, such as histone modifications, can play a role in determining altered cell and production characteristics. Epigenetic control is mainly achieved by DNA-methylation and modifications of histones. The main effect of these modifications is a change in chromatin structure, influencing the transcriptional machinery at the respective locus. So far, there is very little information available about changes in epigenetic regulation in cells in response to altered substrate availability and culture environment. Here we examine the gene transcription pattern and the chromatin states throughout a batch culture, using RNA-seq every 24 hours as well as chromatin immunoprecipitation and sequencing (ChIP-seq) based on antibodies against 6 histone modifications every 12 hours. These histone modifications were the same as described in the International Human Epigenome Consortium (H3K4me3, H3K4me1, H3K27ac, H3K36me3, H3K27me3 and H3K9me3). In addition, DNA-methylation patterns at exponential and stationary growth phase were determined. Both transcription and chromatin modifications during different growth phases are highly dynamic, characterized by a gradual and continuous adaptation to the changing substrate and waste concentrations in the culture. Direct impact of chromatin modifications on the function of co-regulated genes as well as the temporal association between transcription and chromatin state is observed, with special focus on modifications that link to gene expression. Apart from the results on epigenetic regulation, the complete data set has been a valuable resource to improve not only the annotation of the reference CHO genome with novel sets of coding and non-coding genes, but also with chromatin states. In addition, differential binding analysis in promotor regions for H3K27ac during changing environmental conditions shows the importance of epigenetic regulation for instance in apoptosis pathways. Such insights into short term epigenetic regulation could assist in optimisation of bioprocess strategies and control of cell death

Evaluating Prescription Drug Subsidies for Diabetics: Effects on Medication Adherence and Health Outcomes

"Out-of-pocket drug costs are rising at a rapid rate, including for insulin, a life-saving drug used by 3.1 million diabetics on Medicare. High out-of-pocket drug costs place an accentuated burden on people with diabetes, many of whom have low incomes, prompting debate about how to address the growing cost burden of prescription drugs for vulnerable populations. In this project, we propose to evaluate the impact of prescription drug subsidies provided through the Medicare Part D Low-Income Subsidy (LIS) program, which reduces prescription drug co-pays and caps out-of-pocket costs for the program’s lowest-income recipients. Our study will employ a quasi-experimental regression discontinuity (RD) study design to quantify the impacts of the LIS among low-income Medicare beneficiaries with diabetes. Specifically, our RD design will compare diabetic beneficiaries whose income is below LIS eligibility thresholds, who are either fully or largely insulated from rising out-of-pocket drug costs, to diabetic beneficiaries whose income is slightly above these eligibility thresholds, who pay a much larger proportion of prescription drug costs out of pocket and have no limit on their Part D out-of-pocket spending. We will examine whether sizeable differences in out-of-pocket costs associated with these LIS eligibility thresholds are linked to differences in medication adherence and diabetes-related hospitalizations. Thus, our research will provide new evidence about the consequences of high out-of-pocket drug costs for low-income, chronically ill patients and the LIS’s effectiveness in mitigating these costs. This study builds on the co-investigators’ research expertise in pharmaceutical pricing, health insurance policy, and health economics. Seed funds provided through this grant will allow us to pilot our proposed RD design in a large, clinically and economically vulnerable population, establishing the feasibility of our methods to support future extramurally funded research examining policies to improve prescription drug affordability for low-income, aging, and disabled populations.

Evaluating the safety and effectiveness of non-vitamin K antagonist oral anticoagulants in the medicare population

For decades, warfarin was the only oral anticoagulant available for the prevention of stroke and systemic embolism in atrial fibrillation. Since 2010, four non-vitamin K antagonist oral anticoagulant agents have gained Food and Drug Administration approval for this indication: dabigatran, rivaroxaban, apixaban and edoxaban. Chapter 1 provides an introduction to the three research manuscripts that constitute this dissertation. It reviews the use of anticoagulation therapy in atrial fibrillation and especially the evidence on non-vitamin K antagonist oral anticoagulants. Chapter 2 (Manuscript 1) is a retrospective cohort study that compares the risk of stroke and bleeding with rivaroxaban 20mg/dabigatran 150mg, and rivaroxaban 15mg/dabigatran 75mg. This study found no difference in the risk of stroke between dabigatran and rivaroxaban; however, rivaroxaban 20mg and rivaroxaban 15mg were associated with higher risk of thromboembolic events other than stroke, death, major bleeding, and any bleeding events than dabigatran 150mg and dabigatran 75mg. Chapter 3 (Manuscript 2) evaluates the patterns of anticoagulation use after a first major bleeding on dabigatran or warfarin, and compares the thromboembolic and bleeding risk between post-hemorrhage treatment groups. In this study, post-hemorrhage resumption of anticoagulation with either dabigatran or warfarin was associated with increased survival and stroke-free survival, as compared to discontinuing anticoagulation. In addition, this paper revealed that the risk of recurrent major hemorrhage was higher with warfarin than dabigatran. Chapter 4 (Manuscript 3) is a cost-effectiveness study that compares edoxaban 60mg, apixaban 5mg, dabigatran 150mg, dabigatran 110mg, rivaroxaban 20mg and dose-adjusted warfarin in the prevention of stroke in atrial fibrillation patients with high risk of bleeding, as defined by HAS-BLED score ≥3. This study found that, while apixaban 5mg was the most effective strategy, its incremental cost-effectiveness ratio when compared to edoxaban was slightly above the $100,000 per quality-adjusted life year threshold. Public Health Significance The investigations reported in this dissertation will guide clinicians in the prescription of the most appropriate anticoagulation agent according to the clinical characteristics of atrial fibrillation patients. This will ultimately lead to the prevention of strokes, the second leading cause of mortality worldwide, and bleeding events, the most common complication of anticoagulation therapy

Targeted epigenetic glyco-engineering in CHO cells

Extensive knowledge has been gathered by applying and generating –omics techniques and data towards a holistic understanding of the Chinese Hamster Ovary (CHO) cell’s regulatory network. However, these data are far from universally explanatory. The epigenome, i.e. the genetic signature that controls modulation of gene expression, has not yet been fully explored. To enable direct control of epigenetic regulation of individual genes, we constructed CRISPR-based epigenetic editing tools that induce site-specific DNA methylation or demethylation rather than double strand breaks at specific endogenous promoters. The current design targets the promoter of the silenced α (2,6)-sialyltransferase (ST6GAL1) gene, which is actively transcribed in human and there part of the protein glycosylation machinery. It is present in the CHO genome, but silenced. We aimed to induce its expression in CHO by targeted demethylation of the ST6GAL1 promoter. Flow cytometric analysis (based on glycosylation specific lectin staining) showed upregulation of ST6GAL1 in up to 67% of cells in transfected cell pools. ST6GAL1 expression was also confirmed by RT-qPCR and MS glycan analysis. Stable upregulation of ST6GAL1 was monitored over a period of more than 80 days, showing the applicability in industrial cell development pipelines for long-term changes in cell behavior. The effect could be readily reversed by subsequent targeted re-methylation of the ST6GAL1 promoter by our epigenetic editing tool set. In conclusion, this epigenetic tool does not only allow to build a new layer of cell control that complements existing techniques (e.g. genome engineering), but also enables a more sensitive investigation of gene function by induction and repression of genes without altering the DNA sequence. Finally, other than gene knockout or overexpression studies, the modulation is readily reversible, thus opening up a multitude of possibilities for fast, unbiased and stable testing of gene function and multiplex engineering approaches

Association of research and development investments with treatment costs for new drugs approved from 2009 to 2018

Importance Drug companies frequently claim that high prices are needed to recoup spending on research and development. If high research and development costs justified high drug prices, then an association between these 2 measures would be expected. Objective To examine the association between treatment costs and research and development investments for new therapeutic agents approved by the US Food and Drug Administration (FDA) from 2009 to 2018. Design, Setting, and Participants This cross-sectional study analyzed 60 drugs approved by the FDA between January 1, 2009, and December 31, 2018, for which data on research and development investments and list or net prices were available. Data sources included the FDA and SSR Health databases. Main Outcomes and Measures The primary independent variable was estimated research and development investment. The outcome was standardized treatment costs (ie, annual treatment costs for both chronic and cycle drugs, and treatment costs for the maximum length of treatment recommended for acute drugs). Standardized treatment costs were estimated separately using list and net prices obtained from SSR Health at the time of launch and in 2021. To test the association between research and development investments and treatment costs, correlation coefficients were estimated and linear regression models were fitted that controlled for other factors that were associated with treatment costs, such as orphan status. Two models were used: a fully adjusted model that was adjusted for all variables in the data set associated with treatment costs and a parsimonious model in which highly correlated variables were excluded. Results No correlation was observed between estimated research and development investments and log-adjusted treatment costs based on list prices at launch (R = −0.02 and R2 = 0.0005; P = .87) or net prices 1 year after launch (R = 0.08 and R2 = 0.007; P = .73). This result held when 2021 prices were used to estimate treatment costs. The linear regression models showed no association between estimated research and development investments and log-adjusted treatment costs at launch (β = 0.002 [95% CI, −0.02 to 0.02; P = .84] in the fully adjusted model; β = 0.01 [95% CI, −0.01 to 0.03; P = .46] in the parsimonious model) or from 2021 (β = −0.01 [95% CI, −0.03 to 0.01; P = .30] in the fully adjusted model; β = −0.004 [95% CI, −0.02 to 0.02; P = .66] in the parsimonious model). Conclusions and Relevance Results of this study indicated that research and development investments did not explain the variation in list prices for the 60 drugs in this sample. Drug companies should make further data available to support their claims that high drug prices are needed to recover research and development investments, if they are to continue to use this argument to justify high prices

Silver nanoparticle-cellulose composite for thin-film microextraction of Cd and Pb as dithiocarbamate derivatives followed by inductively-coupled plasma mass spectrometry determination

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGPreconcentration of Cd and Pb at ultratrace level in waters following filtration through silver nanoparticles-cellulose composites used for thin-film microextraction was performed. The new procedure was based on the formation of pyrrolidine dithiocarbamate (APDC) derivatives, which showed a large affinity toward the AgNPs. For this purpose, cellulose filters modified with AgNPs were prepared in situ upon reduction of silver ions by sodium tetrahydroborate. The effect of several experimental parameters such as the kind of derivatization agent and its concentration, sample pH, desorption conditions and volume of filtered sample was assessed. Cd and Pb were quantitated in the eluates by inductively coupled plasma-mass spectrometry (ICP-MS). Filters were characterized by scanning electron microscopy (SEM) in backscattering electron mode and combined with energy dispersive X-ray spectrometry, showing the presence of Ag and S in the cellulose filter. The repeatability expressed as relative standard deviation (RSD,%) was 1.4% for Cd and 5.8% for Pb. Methodological detection limits were 0.6 and 8.5 ng/L for Cd and Pb, respectively. The method was applied to several environmental waters.Agencia Estatal de Investigación | Ref. RTI2018-093697-B-I0

Xanthinuria: a rare cause of urolithiasis in the cat

Xanthinuria is a very rare disease in cats. Its etiology may have a genetic origin or may be due to an iatrogenic xan- thine-dehydrogenase inhibition that nally results in urolithiasis. The present work reports two cases of xanthine uro- lithiasis in European Shorthair unrelated male and female cats. Both uroliths were analyzed by stereoscopic microsco- py, infrared spectroscopy and scanning electron microscopy. Besides the report of these two clinical cases, a detailed pathophysiologic review and some updated recommendations for diagnosis and treatment for this condition were done.La xantinuria es una patología que se presenta raramente en los gatos. Su etiología puede tener origen genético o de- berse a una inhibición yatrogénica de la enzima xantina deshidrogenasa, que generalmente se mani esta con urolitiasis. En este trabajo se informa el hallazgo de dos urolitos de xantina en dos gatos, un macho y una hembra, de raza Euro- pea de pelo corto, no emparentados. Los urolitos fueron analizados mediante microscopía estereoscópica, espectrosco- pía infrarroja y microscopía electrónica de barrido. Además de informar sobre estos casos clínicos, se hace una revisión detallada de la siopatología y de las recomendaciones actuales para el diagnóstico y manejo médico de esta patología.Se agradece al Consejo Nacional de Ciencia y Tecnolo- gía de México (CONACyT) y al Programa de Mejora- miento del Profesorado de la Secretaria de Educación Pública de México 2011 (PROMEP-SEP), el apoyo complementario para la realización de este trabajo

A myxoid fibrotic reaction pattern is associated with metastatic risk in cutaneous squamous cell carcinoma

Metastasis; Fibrosis; Cutaneous squamous cell carcinomaMetástasis; Fibrosis; Carcinoma cutáneo de células escamosasMetàstasi; Fibrosi; Carcinoma cutani de cèl·lules escamosesAlthough desmoplasia has been associated with poor prognoses in cutaneous squamous cell carcinoma, little attention has been paid to the patterns of fibrosis. This study aimed to examine the different stromal fibrotic patterns as markers of metastatic risk. We performed a multicenter retrospective study that included 102 cutaneous squamous cell carcinomas (52 non-metastatic and 50 metastatic carcinomas). Clinical and histopa-thological data were registered. The fibrotic reaction pattern was classified as mature, intermediate or immature depending on the presence of keloid-like collagen and myxoid stroma. The immature pattern (areas characterized by myxoid changes with no inflammation) was observed in 18 samples and its presence was significantly associated with immuno-suppression, budding, desmoplasia, perineural invasion, anatomic level, tumoural depth and metastatic risk in the multivariate analysis. Our findings suggest that the presence of an immature myxoid fibrotic pattern, which can be easily identified by routine hematoxylin-eosin staining, is strongly associated with metastatic risk.This work has been supported by grant PI15/00236 from Fondo de Investigación Sanitaria (FIS), Fondo Europeo de Desarrollo Regional (FEDER), Instituto de Salud Carlos III, Ministerio de Sanidad, and the ‘‘Xarxa de Bancs de Tumours”