Electrophoretic mobility of supercoiled, catenated and knotted DNA molecules.

We systematically varied conditions of two-dimensional (2D) agarose gel electrophoresis to optimize separation of DNA topoisomers that differ either by the extent of knotting, the extent of catenation or the extent of supercoiling. To this aim we compared electrophoretic behavior of three different families of DNA topoisomers: (i) supercoiled DNA molecules, where supercoiling covered the range extending from covalently closed relaxed up to naturally supercoiled DNA molecules; (ii) postreplicative catenanes with catenation number increasing from 1 to ∼15, where both catenated rings were nicked; (iii) knotted but nicked DNA molecules with a naturally arising spectrum of knots. For better comparison, we studied topoisomer families where each member had the same total molecular mass. For knotted and supercoiled molecules, we analyzed dimeric plasmids whereas catenanes were composed of monomeric forms of the same plasmid. We observed that catenated, knotted and supercoiled families of topoisomers showed different reactions to changes of agarose concentration and voltage during electrophoresis. These differences permitted us to optimize conditions for their separation and shed light on physical characteristics of these different types of DNA topoisomers during electrophoresis

Study of caveolin-1 gene expression in whole adipose tissue and its subfractions and during differentiation of human adipocytes

Caveolins are 21-24 kDa integral membrane proteins that serve as scaffolds to recruit numerous signaling molecules. Specific subclasses of caveolae carry out specific functions in cell metabolism. In particular, triglycerides are synthesized at the site of fatty acid entry in one of these caveolae classes. OBJECTIVE AND METHODS: We studied the expression of caveolin-1 (CAV-1) gene in association with metabolic variables in 90 visceral and 55 subcutaneous adipose tissue samples from subjects with a wide range of fat mass, in the stromovascular fraction (SVC) and isolated adipocytes, and during differentiation of human adipocytes. RESULTS: CAV-1 gene expression was significantly decreased in visceral adipose tissue (v-CAV-1) of obese subjects. v-CAV-1 was positively associated with several lipogenic genes such as acetyl-coA carboxylase (ACACA, r = 0.34, p = 0.004) and spot-14 (r = 0.33, p = 0.004). In non-obese subjects v-CAV-1 also correlated with fatty acid synthase (FAS, r = 0.60, p < 0.0001). Subcutaneous (sc) adipose tissue (sc-CAV-1) gene expression was not associated with these lipogenic factors when obese and non-obese subjects were studied together. In obese subjects, however, sc-CAV-1 was associated with fatty acid synthase (FAS, r = 0.36, p = 0.02), sterol regulatory element binding protein-1c (SREBP-1c (r = 0.58, p < 0.0001), ACACA (r = 0.33, p = 0.03), spot-14 (r = 0.36, p = 0.02), PPAR-gamma co-activator-1 (PGC-1, r = 0.88, n = 19). In these obese subjects, sc-CAV-1 was also associated with fasting triglycerides (r = -0.50, p < 0.0001).CAV-1 expression in mature adipocytes was significantly higher than in stromal vascular cells. CAV-1 gene expression in adipocytes from subcutaneous adipose tissue (but not in adipocytes from visceral adipose tissue) was significatively associated with fasting triglycerides. CAV-1 gene expression did not change significantly during differentiation of human preadipocytes from lean or obese subjects despite significant increase of FAS gene expression. CONCLUSION: Decreased CAV-1 gene expression was simultaneously linked to increased triglycerides and decreased lipogenic gene expression among obese subjects, paralleling the observations of hypertriglyceridemia in CAV-1 knockout mice. However, the regulation of CAV-1 gene expression seems independent of the adipogenic program

Actitudes y percepciones de los docentes universitarios en el proceso de adopción de una innovación. La iniciativa OpenCourseWare en la Universidad de Valencia (España)

El proyecto OpenCourseWare, repositorio de recursos educativos en abierto, se inició en la Universidad de Valencia en 2008 y en 2009, sólo incluía 10 asignaturas, ninguna de ellas del área de ciencias de la salud. El objetivo de este trabajo es investigar las actitudes de los docentes de esta área así como sus percepciones con relación a este repositorio para determinar cuáles son las estrategias necesarias para extender su uso. Se parte de la teoría de la difusión de las innovaciones de Rogers (2003) y de un enfoque cualitativo a través del muestreo teórico, entrevistas semiestructuradas y codificación abierta. Los resultados indican la existencia de dos grandes grupos de profesores. Los adoptantes tempranos con una predisposición alta a participar en la iniciativa y con una percepción positiva de sus atributos y los mainstream o corriente principal más reacios a participar y con una percepción negativa respecto a alguno de sus atributos. La identificación de las características de estos dos grandes grupos marca las líneas de acción y de investigación futura en el ámbito del marketing y difusión, formación, sensibilización y motivación para extender el uso del OCW. The OpenCourseWare project, an open learning resource repository, was set up at the University of Valencia between 2008 and 2009. It initially consisted of only 10 subjects, none of which was in the field of health sciences. The objective of this research is to investigate the attitudes and perceptions of teaching staff in the field of health sciences with regard to the project in order to identify strategies to increase its use and expand its coverage. The diffusion of innovations theory as propounded by Rogers is used, along with a qualitative approach using theoretical sampling, semi-structured interviews and open coding. The results indicate the existence of two categories of teaching staff. Firstly, those who adopt an innovation early, have a marked inclination to participate in the initiative and a positive perception of the characteristics of the innovation. Secondly, a larger category of those more reluctant to participate in it and with a negative perception of one or more of its characteristics. Identifying the nature of these two groups provides guidelines for future action and research in the marketing and distribution of such projects, and the training, awareness and motivation required in order to extend the use of OCW

Impact of COVID-19 on Formal Education: An International Review of Practices and Potentials of Open Education at a Distance.

In terms of scale, shock, and disenfranchisement, the disruption to formal education arising from COVID-19 has been unprecedented. Anecdotally, responses from teachers and educators around the world range from heightened caution to being inspired by distance education as the 'new normal.' Of all the challenges, face-to-face and formal teaching have been most heavily affected. Despite some education systems demonstrating resilience, a major challenge is sustaining quality and inclusiveness in formal education suddenly delivered at a distance. In probing these issues, this article profiles international perspectives on the role of open education in responding to the impact on formal school and higher education caused by the COVID-19 pandemic. We proceed by highlighting and analysing practices and case studies from 13 countries representing all global regions, identifying and discussing the challenges and opportunities that have presented themselves. Reports cover the period from the beginning of 2020 until 11 March 2021, the first anniversary of the COVID-19 outbreak as declared by the World Health Organization. In our comparative study, we identify seven key aspects of which three (missing infrastructure and sharing OER, open education and access to OER, and urgent need for professional development and training for teachers) are directly related to open education at a distance. After comparing examples of existing practice, we make recommendations and offer insights into how open education strategies can lead to interventions that are effective and innovative¿to improve formal education at a distance in schools and universities in the future

Efecto sobre la mortalidad de la ampliación a los festivos y fines de semana del proyecto "UCI sin paredes". Estudio before-after.

Objetivo: Estudiar si la ampliación, a festivos y fines de semana, del protocolo de detección proactiva precoz de gravedad en el hospital y actuación de intensivistas en planta convencional y urgencias (actividad «UCI sin paredes») se asocia a una reducción en la mortalidad de los pacientes ingresados en UCI en esos días. Diseno: ˜ Estudio cuasiexperimental before---after. Ámbito: Hospital de nivel 2 con 210 camas en funcionamiento y UCI polivalente con 8 camas. Pacientes o participantes: En el grupo control, donde no se realiza la actividad «UCI sin paredes» los fines de semana ni festivos, se incluyeron los pacientes ingresados en la UCI esos días del 1 de enero de 2010 al 30 de abril de 2013. En el grupo intervención se amplió la actividad «UCI sin paredes» a los fines de semana y festivos y se incluyeron los pacientes ingresados esos días del 1 de mayo de 2013 al 31 de octubre de 2014. Se excluyeron los pacientes procedentes de quirófano tras una cirugía programada. Variables de interés: Se analizaron las variables demográficas (edad, sexo), la procedencia (urgencias, planta de hospitalización, quirófano), el tipo de paciente (médico, quirúrgico), el motivo de ingreso, las comorbilidades y el SAPS 3 como puntuación de gravedad al ingreso, estancia en UCI y hospitalaria, además de la mortalidad en la UCI y en el hospital. Resultados: Se incluyeron en el grupo control 389 pacientes, y 161 en el grupo intervención. No se encontraron diferencias entre ambos grupos, salvo en la comorbilidad cardiovascular (un 49% en el grupo control frente a un 33% en el grupo intervención; p < 0,001), en la gravedad al ingreso medida mediante el SAPS 3 (mediana de 52 [percentiles 25---75: 42---63] en el grupo control frente a 48 [percentiles 25---75: 40---56] en el grupo intervención; p = 0,008) y en la mortalidad en UCI, que fue de un 11% en el grupo control (IC 95% 8 a 14) frente al 3% (IC 95% 1 a 7) en el grupo intervención (p = 0,003). En el análisis multivariable, los 2 únicos factores asociados con la mortalidad en UCI fueron: SAPS 3 (OR 1,08; IC 95% 1,06---1,11) y el pertenecer al grupo intervención (OR 0,33; IC 95% 0,12---0,89). Conclusiones: La ampliación de la actividad «UCI sin paredes» a los fines de semana y festivos conlleva un descenso en la mortalidad en la UCI.Objective: To determine whether extension to holidays and weekends of the protocol for the early proactive detection of severity in hospital (‘‘ICU without walls’’ project) results in decreased mortality among patients admitted to the ICU during those days. Design: A quasi-experimental before---after study was carried out. Setting: A level 2 hospital with 210 beds and a polyvalent ICU with 8 beds. Patients or participants: The control group involved no ‘‘ICU without walls’’ activity on holidays or weekends and included those patients admitted to the ICU on those days between 1 January 2010 and 30 April 2013. The intervention group in turn extended the ‘‘ICU without walls’’ activity to holidays and weekends, and included those patients admitted on those days between 1 May 2013 and 31 October 2014. Patients arriving from the operating room after scheduled surgery were excluded. Variables of interest: An analysis was made of the demographic variables (age, gender), origin (emergency room, hospital ward, operating room), type of patient (medical, surgical), reason for admission, comorbidities and SAPS 3 score as a measure of severity upon admission, stay in the ICU and in hospital, and mortality in the ICU and in hospital. Results: A total of 389 and 161 patients were included in the control group and intervention group, respectively. There were no differences between the 2 groups except as regards cardiovascular comorbidity (49% in the control group versus 33% in the intervention group; P < .001), severity upon admission (median SAPS 3 score 52 [percentiles 25---75: 42---63) in the control group versus 48 [percentiles 25---75: 40---56] in the intervention group; P = .008) and mortality in the ICU (11% in the control group [95% CI 8---14] versus 3% [95% CI 1---7] in the intervention group; P = .003). In the multivariate analysis, the only 2 factors associated to mortality in the ICU were the SAPS 3 score (OR 1.08; 95% CI 1.06---1.11) and inclusion in the intervention group (OR 0.33; 95% CI 0.12---0.89). Conclusions: Extension of the ‘‘ICU without walls’’ activity to holidays and weekends results in a decrease in mortality in the ICU.pre-print424 K

A Proposed Approach to Chronic Airway Disease (CAD) Using Therapeutic Goals and Treatable Traits: A Look to the Future

© 2020 Pérez de Llano et al.Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) – understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis

3D magnetic configuration of ferrimagnetic multilayers with competing interactions visualized by soft X ray vector tomography

Full control of magnetic properties in exchange coupled systems requires a good understanding of 3D magnetic configuration with lateral and in depth resolution. Here we show results from a soft X ray tomographic reconstruction which allow determining, solely from the experimental data, a detailed description of the vector magnetic configuration of a ferrimagnetic Gd12Co88 Nd17Co83 Gd24Co76 trilayer with engineered competing anisotropy, exchange and magneto static interactions at different depths. The trilayer displays chevron patterns with a distorted closure structure. Near the top Gd24Co76 layer, local exchange springs with out of plane magnetization reversal, quasi domains with ripple like patterns and magnetic vortices and antivortices across the thickness are observed. The detailed analysis of the magnetic tomogram shows that the effective strength of the exchange spring at the NdCo GdCo interface can be finely tuned by GdxCo1 x composition and anisotropy determined by sample fabrication and in plane stripe orientation adjustable , demonstrating the suitability of 3D magnetic visualization techniques in magnetic engineering researc

Impact of COVID-19 on Formal Education: An International Review of Practices and Potentials of Open Education at a Distance

In terms of scale, shock, and disenfranchisement, the disruption to formal education arising from COVID-19 has been unprecedented. Anecdotally, responses from teachers and educators around the world range from heightened caution to being inspired by distance education as the “new normal.” Of all the challenges, face-to-face and formal teaching have been most heavily affected. Despite some education systems demonstrating resilience, a major challenge is sustaining quality and inclusiveness in formal education suddenly delivered at a distance. In probing these issues, this article profiles international perspectives on the role of open education in responding to the impact on formal school and higher education caused by the COVID-19 pandemic. We proceed by highlighting and analysing practices and case studies from 13 countries representing all global regions, identifying and discussing the challenges and opportunities that have presented themselves. Reports cover the period from the beginning of 2020 until 11 March 2021, the first anniversary of the COVID-19 outbreak as declared by the World Health Organization. In our comparative study, we identify seven key aspects of which three (missing infrastructure and sharing OER, open education and access to OER, and urgent need for professional development and training for teachers) are directly related to open education at a distance. After comparing examples of existing practice, we make recommendations and offer insights into how open education strategies can lead to interventions that are effective and innovative—to improve formal education at a distance in schools and universities in the future

Model-observations synergy in the coastal ocean

Integration of observations of the coastal ocean continuum, from regional oceans to shelf seas and estuaries/deltas with models, can substantially increase the value of observations and enable a wealth of applications. In particular, models can play a critical role at connecting sparse observations, synthesizing them, and assisting the design of observational networks; in turn, whenever available, observations can guide coastal model development. Coastal observations should sample the two-way interactions between nearshore, estuarine and shelf processes and open ocean processes, while accounting for the different pace of circulation drivers, such as the fast atmospheric, hydrological and tidal processes and the slower general ocean circulation and climate scales. Because of these challenges, high-resolution models can serve as connectors and integrators of coastal continuum observations. Data assimilation approaches can provide quantitative, validated estimates of Essential Ocean Variables in the coastal continuum, adding scientific and socioeconomic value to observations through applications (e.g., sea-level rise monitoring, coastal management under a sustainable ecosystem approach, aquaculture, dredging, transport and fate of pollutants, maritime safety, hazards under natural variability or climate change). We strongly recommend an internationally coordinated approach in support of the proper integration of global and coastal continuum scales, as well as for critical tasks such as community-agreed bathymetry and coastline products

Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project

Purpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection