A Portable, Neurostimulation-Integrated, Force Measurement Platform for the Clinical Assessment of Plantarflexor Central Drive.

Plantarflexor central drive is a promising biomarker of neuromotor impairment; however, routine clinical assessment is hindered by the unavailability of force measurement systems with integrated neurostimulation capabilities. In this study, we evaluate the accuracy of a portable, neurostimulation-integrated, plantarflexor force measurement system we developed to facilitate the assessment of plantarflexor neuromotor function in clinical settings. Two experiments were conducted with the Central Drive System (CEDRS). To evaluate accuracy, experiment #1 included 16 neurotypical adults and used intra-class correlation (ICC2,1) to test agreement of plantarflexor strength capacity measured with CEDRS versus a stationary dynamometer. To evaluate validity, experiment #2 added 26 individuals with post-stroke hemiparesis and used one-way ANOVAs to test for between-limb differences in CEDRS' measurements of plantarflexor neuromotor function, comparing neurotypical, non-paretic, and paretic limb measurements. The association between paretic plantarflexor neuromotor function and walking function outcomes derived from the six-minute walk test (6MWT) were also evaluated. CEDRS' measurements of plantarflexor neuromotor function showed high agreement with measurements made by the stationary dynamometer (ICC = 0.83, p < 0.001). CEDRS' measurements also showed the expected between-limb differences (p's < 0.001) in maximum voluntary strength (Neurotypical: 76.21 ± 13.84 ft-lbs., Non-paretic: 56.93 ± 17.75 ft-lbs., and Paretic: 31.51 ± 14.08 ft-lbs.), strength capacity (Neurotypical: 76.47 ± 13.59 ft-lbs., Non-paretic: 64.08 ± 14.50 ft-lbs., and Paretic: 44.55 ± 14.23 ft-lbs.), and central drive (Neurotypical: 88.73 ± 1.71%, Non-paretic: 73.66% ± 17.74%, and Paretic: 52.04% ± 20.22%). CEDRS-measured plantarflexor central drive was moderately correlated with 6MWT total distance (r = 0.69, p < 0.001) and distance-induced changes in speed (r = 0.61, p = 0.002). CEDRS is a clinician-operated, portable, neurostimulation-integrated force measurement platform that produces accurate measurements of plantarflexor neuromotor function that are associated with post-stroke walking ability.

Investigating Changes in Muscle Coordination During Cycling with Soft Wearable Strain Sensors Sensitive to Muscle Deformation.

Continuous monitoring of muscle coordination can provide valuable information regarding an individual's performance during physical activities. For example, changes in muscle coordination can indicate muscle fatigue during exhaustive exercise or can be used to track the rehabilitation progress of patients post-injury. Traditional methods to evaluate coordination often focus solely on measuring muscle activation with electromyography, ignoring timing changes of the resultant force produced by the activated muscle. Setups designed to evaluate force directly to study muscle coordination are often limited by either hyper-constrained settings or cost-prohibitive hardware. In this paper, we employ wearable, ultra-sensitive soft strain sensors that track muscle deformation for estimating changes in muscle coordination during cycling at different cadences and to exhaustion. The results were compared to muscle activation timing measured by electromyography and peak force timing measured by a cycle ergometer. We demonstrate that with an increase in cadence, the soft strain sensor and ergometer timing metrics align more closely than those measured by electromyography. We also demonstrate how muscle coordination is altered with the onset of fatigue during cycling to exhaustion.

Programmable soft valves for digital and analog control.

In soft devices, complex actuation sequences and precise force control typically require hard electronic valves and microcontrollers. Existing designs for entirely soft pneumatic control systems are capable of either digital or analog operation, but not both, and are limited by speed of actuation, range of pressure, time required for fabrication, or loss of power through pull-down resistors. Using the nonlinear mechanics intrinsic to structures composed of soft materials-in this case, by leveraging membrane inversion and tube kinking-two modular soft components are developed: a piston actuator and a bistable pneumatic switch. These two components combine to create valves capable of analog pressure regulation, simplified digital logic, controlled oscillation, nonvolatile memory storage, linear actuation, and interfacing with human users in both digital and analog formats. Three demonstrations showcase the capabilities of systems constructed from these valves: 1) a wearable glove capable of analog control of a soft artificial robotic hand based on input from a human user's fingers, 2) a human-controlled cushion matrix designed for use in medical care, and 3) an untethered robot which travels a distance dynamically programmed at the time of operation to retrieve an object. This work illustrates pathways for complementary digital and analog control of soft robots using a unified valve design.

Air Pollution and the Effectiveness of Positive Airway Pressure Therapy in Individuals With Sleep Apnea: A Retrospective Community-Based Repeated-Measures Longitudinal Study.

BACKGROUND: Ambient air pollution may affect the severity of untreated OSA, but it is unknown whether air pollution adversely impacts the effectiveness of positive airway pressure (PAP) therapy. RESEARCH QUESTION: Do short-term changes in outdoor air pollution adversely impact adults with OSA using PAP therapy? STUDY DESIGN AND METHODS: We conducted a retrospective community-based repeated-measures longitudinal study of adults with OSA who purchased a PAP device from a registered equipment provider between 2013 and 2017 (Ontario, Canada) and had data on the daily device-derived residual apnea-hypopnea index (AHIFlow). We linked daily PAP-derived data to air pollution databases using postal codes. The primary exposures were mean nocturnal (8 pm to 8 am) residential concentrations of ozone, fine particulate matter, nitrogen dioxide, carbon monoxide, sulfur dioxide, and the Air Quality Health Index (AQHI). Potential confounders considered were demographics, season and year of exposure, initial OSA severity, other PAP parameters, and climate-related variables. RESULTS: Eight thousand one hundred forty-eight adults were analyzed with a median of 89 days (interquartile range [IQR], 29-302 days) of observation during which PAP was used for ≥ 4 h. The median daily AHIFlow was 1.2/h (IQR, 0.5-2.5/h). In mixed multivariate regression analyses, an increase in air pollution was associated with a statistically significant increase in AHIFlow for most statistical models. The largest effect was for the AQHI: an increase in AHIFlow while comparing highest vs lowest quartiles was 0.07/h (95% CI, 0.05-0.10/h). INTERPRETATION: We demonstrated a modest but statistically significant increase in residual respiratory events during PAP therapy associated with an increase in air pollution concentrations.

Toward Soft Wearable Strain Sensors for Muscle Activity Monitoring.

The force-generating capacity of skeletal muscle is an important metric in the evaluation and diagnosis of musculoskeletal health. Measuring changes in muscle force exertion is essential for tracking the progress of athletes during training, for evaluating patients' recovery after muscle injury, and also for assisting the diagnosis of conditions such as muscular dystrophy, multiple sclerosis, or Parkinson's disease. Traditional hardware for strength evaluation requires technical training for operation, generates discrete time points for muscle assessment, and is implemented in controlled settings. The ability to continuously monitor muscle force without restricting the range of motion or adapting the exercise protocol to suit specific hardware would allow for a richer dataset that can help unlock critical features of muscle health and strength evaluation. In this paper, we employ wearable, ultra-sensitive soft strain sensors for tracking changes in muscle deformation during contractions. We demonstrate the sensors' sensitivity to isometric contractions, as well as the sensors' capacity to track changes in peak torque over the course of an isokinetic fatiguing protocol for the knee extensors. The wearable soft system was able to efficiently estimate peak joint torque reduction caused by muscle fatigue (mean NRMSE = 0.15±0.03 ).

Demographics, sleep apnea and positive airway pressure (PAP) treatment-related characteristics associated with PAP adherence: A large retrospective community-based longitudinal observational study.

OBJECTIVE/BACKGROUND: Despite many years of research, multiple factors have inconsistently shown to be associated with positive airway pressure (PAP) adherence. We conducted a retrospective observational study to evaluate the association between selected demographics, obstructive sleep apnea (OSA) - and generally available PAP treatment-related factors with objective PAP therapy adherence. PATIENTS/METHODS: We considered all consented individuals with OSA who purchased a PAP device from a registered vendor (Ottawa, Ontario) between 2011 and 2017 who had usage data available (n = 11,614). PAP adherence was measured objectively as PAP use for at least 4 h on at least 70% of days on treatment. RESULTS: In our cohort, 7147 (61.5%) participants were deemed adherent to PAP over a median of 214 days (IQR: 84-675). The median percentage of days PAP therapy was used was 82% (IQR: 48-97%), and the median number of days PAP therapy was used for greater than 4 h was 95 (IQR: 28-372). In multivariable logistic regression considering all variables available, increased body mass index, older age, and lower minimum SaO2 at baseline sleep study were significantly associated with increased PAP adherence. Individuals who were using PAP longer and with greater adherence during the first month were subsequently more adherent to therapy. We also found a different predictive ability of PAP adherence-related factors by age and sex. CONCLUSIONS: In this retrospective community-based longitudinal observational study, we identified readily available demographics and OSA-related factors associated with PAP adherence. We also confirmed previous findings on age and sex disparities in adherence to PAP.

Tracking changes in national BCG vaccination policies and practices using the BCG World Atlas.

The BCG vaccine is a widely given vaccine against tuberculosis (TB), yet studies on effectiveness have shown considerable heterogeneity; as a result, BCG vaccine policies vary greatly across the globe and change across geography, and with time and disease burden. The recently updated third BCG World Atlas (www.bcgatlas.org) is a publicly available online database with information on BCG practices across 194 countries. This helpful resource has been used for over 10 years to support clinicians, TB researchers and TB vaccine development worldwide. Here, we summarise main findings from the third BCG Atlas' most recent update which included additional data collected around BCG strain type, vaccine stockouts and associated changes. Longitudinal analysis enables evaluation of changes in TB incidence over time, a method becoming more common in legislation interventions. A large number of countries in the BCG Atlas (156/194 countries) maintain universal neonatal BCG vaccination, of which 51 are considered low TB burden countries. We demonstrate the majority of countries who changed their national policy moved to targeted vaccination for high-risk groups, were in Europe and also had significant decreases in TB incidence both before and after policy change. Globally, the most common BCG strain continues to be the Danish strain, despite its worldwide manufacturing interruption in 2015. Substantial variation and disproportionality exists in which regions were most affected by stockouts between 2009 and 2019. Tracking and understanding the reasoning behind changes to national BCG practices and their impact on TB burden is critical for decision makers as they contemplate how to include BCG vaccination in future immunisation guidelines in low and high TB burden countries.

Skeletal muscle regeneration with robotic actuation-mediated clearance of neutrophils.

Mechanical stimulation (mechanotherapy) can promote skeletal muscle repair, but a lack of reproducible protocols and mechanistic understanding of the relation between mechanical cues and tissue regeneration limit progress in this field. To address these gaps, we developed a robotic device equipped with real-time force control and compatible with ultrasound imaging for tissue strain analysis. We investigated the hypothesis that specific mechanical loading improves tissue repair by modulating inflammatory responses that regulate skeletal muscle regeneration. We report that cyclic compressive loading within a specific range of forces substantially improves functional recovery of severely injured muscle in mice. This improvement is attributable in part to rapid clearance of neutrophil populations and neutrophil-mediated factors, which otherwise may impede myogenesis. Insights from this work will help advance therapeutic strategies for tissue regeneration broadly.

Neuromielitis óptica: reporte de un caso clínico / Optic neuromyelitis: a clinical case report

La neuromielitis óptica (NMO) y los trastornos del espectro de neuromielitis óptica (NMOSD) son trastornos poco frecuentes, mediados por anticuerpos del sistema nervioso central (SNC) con predilección por la médula espinal y los nervios ópticos. Existe una fuerte predilección femenina. En el caso de la forma recurrente más común de la enfermedad, que representa del 80% al 90% de los casos, las mujeres están sobrerrepresentadas con una proporción de 5 a 10: 1.6. La edad media de inicio es de 39,7 años. Objetivo: Determinar la causa de neuromielitis óptica en paciente femenina de 24 años de edad. Materiales y métodos: Es una investigación enmarcada en el paradigma positivista, con enfoque cuantitativo. Con un estudio de campo-descriptivo, no experimental, en la modalidad de caso clínico único. El método utilizado fue la historia clínica y consentimiento informado. Resultado: Se presenta el caso de una paciente de sexo femenino de 24 años de edad, sin antecedentes patológicos personales. Presentó pérdida progresiva de la visión de 2 meses de evolución, que se acompañaba de dolor en región cervical de moderada intensidad y en 24 horas presentó parestesia en brazo derecho, afasia, cuadro neurológico que evolucionó hasta presentar cuadriparesia, insuficiencia respiratoria aguda. Conclusión: En IRM de columna cervical se evidencia cambio anormal de la señal medular cervical evidente en secuencias T2 flair lesión hiperintensa longitudinalmente extensa que abarca más de 3 cuerpos vertebrales. Fue tratada con corticoides y plasmaféresis(AU)

Neuromielitis optic (NMO) and neuromielitis optic spectrum disorders (NMOSD) are rare disorders mediated by antibodies of the central nervous system (CNS) with a predilection for the spinal cord and optic nerves. There is a strong female predilection. In the case of the most common recurrent form of the disease, which accounts for 80% to 90% most of the cases are women with a ratio of five to 10: 1.6. The mean age of onset is 39.7 years. Objective: To determine the cause of neuromielitis optica in a 24-year-old female patient. Materials and methods: It is an investigation framed in the positivist paradigm, with a quantitative approach. With a descriptive field study, not experimental, in the single clinical case modality. The method used was the medical history and informed consent. Result: The case of a 24-year-old female patient with no presented personal pathological history. She presented progressive loss of vision of 2 months of evolution, accompanied by pain in the cervical region of moderate intensity and within 24 hours, she presented paresthesia in the right arm, aphasia, a neurological picture that evolved until presenting cuadriparesia, acute respiratory failure. Conclusion: An MRI of the cervical spine shows an abnormal change in the cervical spinal signal evident in T2 sequences flair a longitudinally extensive hiperintensa lesion that encompasses more than 3 vertebral bodies. Her treatment was corticosteroids and plasmapheresis(AU)

Decisiones, bienestar y desarrollo humano en departamentos de bienestar estudiantil. Discusión de hallazgos / Decisões, bem-estar e desenvolvimento humano em departamento de bem-estar estudantil. Discussão de resultados / Decisions, well-being and human development in departments of student well-being. Discussion of findings

El presente estudio cualitativo tuvo como objetivo explorar la arquitectura para la toma de decisiones que se promueve en los programas institucionales de bienestar y desarrollo humano, ofrecidos en tres instituciones de educación superior de la ciudad de Medellín y el municipio de Bello en Antioquia, Colombia. Para lograrlo, se conocieron los programas institucionales y se detectaron los componentes asociados con la arquitectura para la toma de decisiones. Se realizaron quince entrevistas semi-estructuradas a líderes encargados de los programas institucionales en las universidades objeto de estudio y un grupo focal con estudiantes universitarios. Para el análisis se utilizó un proceso de codificación y triangulación de las entrevistas. Esta información fue contrastada con la revisión documental y la investigación empírica, las cuales enfatizan la importancia de diseñar contextos para aumentar el bienestar de las personas. Finalmente, sugerimos un programa de formación en toma de decisiones para los arquitectos encargados de estas áreas.

Este estudo qualitativo teve como objetivo explorar a arquitetura para a tomada de decisão promovida nos programas institucionais de bem-estar e desenvolvimento humano, oferecidos em três instituições de ensino superior na cidade de Medellín e no município de Bello, em Antioquia, na Colômbia. Para realizá-lo, foram analisados os programas institucionais e detectados os componentes associados à arquitetura para tomada de decisão. Foram realizado quinze entrevistas semi-estruturadas aos líderes responsáveis dos programas institucionais nas universidades em estudo. Para a análise, foi utilizado um processo de codificação e triangulação das entrevistas. Esta informação foi contrastada com a revisão documental e a pesquisa empírica, que enfatizam a importância de projetar contextos para aumentar o bem-estar das pessoas. Finalmente, sugerimos um programa de Formação na tomada de decisão para os arquitetos responsáveis destas áreas.

The objective of this qualitative study was to explore the architecture for decision making promoted in the institutional programs of welfare and human development, offered in three institutions of higher education in the city of Medellin and the municipality of Bello in Antioquia, Colombia. To achieve this, we got the information about the institutional programs. Then, we extract the components associated with the architecture for decision making. Fifteen semi-structured interviews were carried out with leaders in charge of institutional programs at the universities under study. For the analysis, we used a process of coding and triangulation of the interviews. This information was contrasted with the documentary review and empirical research, which emphasize the importance of designing contexts to increase human well-being. Finally, we suggest a training program in decision making for the architects in charge of these areas.

Libertad y desarrollo humano en las organizaciones / Freedom and human development in organizations

El presente artículo hace una reflexión sobre la implementación del enfoque de desarrollo humano en las organizaciones laborales. Se explicarán los elementos socio-históricos que originaron su creación, el papel del Programa de las Naciones Unidas para el Desarrollo (PNUD) y los principales pilares del paradigma a partir de una discusión teórica del concepto de capacidades. Propone que el enfoque de desarrollo humano, y en particular el de capacidades humanas, tiene diversas aplicaciones en el contexto organizacional, no limitado al desarrollo de competencias laborales. Se reconoce que las capacidades para la vida en común y para la ciudadanía también pueden fortalecerse en el entorno laboral, siendo las organizaciones espacios de interacción social. Una implementación vigorosa de dichos enfoques requiere superar la mirada economicista de las relaciones laborales, dando lugar a que las organizaciones ofrezcan oportunidades reales, incluyendo la libertad de agencia y la decisión subjetiva, como responsabilidad compartida con el desarrollo de las personas.

This article reflects on the implementation of the human development approach in labor organizations. We will explain the socio-historical elements that led to its creation, the role of the United Nations Development Program (UNDP) and the main pillars of the paradigm, base on a theoretical discussion of the concept of capabilities. We propose that the human development approach, and in particular that of human capacities, has diverse applications in the organizational context, not limited to the development of labor competencies. We recognize that the capacities for life in common can be strengthened in the work environment, since the organizations are also spaces of social interaction. Accepting these premises, employees can be educated for citizenship, while acquiring skills for productive life. A vigorous implementation of these approaches requires overcoming the economicist view of labor relations, giving organizations the chance to offer real opportunities, including agency freedom and subjective decision, as a shared responsibility for the development of people. The paradigm of human development has been widely applied in community work because of its impact on the design of public policies and social programs. In the 1980s, the ideas of the Pakistani economist Mahbub ul Haq were materialized in the first Human Development Report. Since 1990, to date, UNDP has continued to publish annual reports. Indian philosopher and economist Amartya Sen contributed to the creation of the Human Development Index; along with the American philosopher Martha Nussbaum have developed proposals to develop capabilities. The authors' work proves a high commitment to freedom, human rights and democracy, bringing the welfare economy to political science, economics and ethics. Although the focus has gained attention in government policies and social institutions, its application in labor organizations has not achieved the same diffusion. Recently, the UNDP Human Development Report 2015 has addressed this issue in studying work and its impact on people. Perhaps its lack of application in the labor organizations is that in these the subject is usually conceived as a means of production, not as an end in itself. Hence, development opportunities are usually measured in criteria of productivity and economic growth of the organization, instead of growth and development of people. This approach initially emerges as a critique of the economic model focused on the production of consumer goods, which sought to bring the benefits of increased output to the lower income groups. Far from enumerating the errors and neglects of the models that have sustained injustice, the approach proposes alternatives to pay for this "social debt" that has left great inequality gaps in the vulnerable population. Since its first report, UNDP has emphasized the importance of offering people and Communities options to economic alternatives for empowerment and the expansion of human freedoms. In this sense, the Human Development approach does not deny the important role that the economic conditions of individual, group or collective subjects fulfill, but its message is broader. While it is true that economic factors help meet the essential needs of men, economic growth has no automatic link with human progress (UNDP, 1990). It does not mean neglecting the GDP indicator, but how to translate that growth into the strengthening of human capabilities. We consider it is the development of the subjects that drives the organization, not viceversa. Therefore, the interest that people have in this proposal is special. The central issues for its implementation require defining this paradigm and its main foundations. For this it is necessary to contrast the concept of human capabilities and their possible equivalent in organizations: labor competencies. Finally, we present the implications of free agency and co-responsibility of organizations, since human development obeys a subjective decision.

Mechanism and catalytic strategy of the prokaryotic-specific GTP cyclohydrolase-IB.

Guanosine 5'-triphosphate (GTP) cyclohydrolase-I (GCYH-I) catalyzes the first step in folic acid biosynthesis in bacteria and plants, biopterin biosynthesis in mammals, and the biosynthesis of 7-deazaguanosine-modified tRNA nucleosides in bacteria and archaea. The type IB GCYH (GCYH-IB) is a prokaryotic-specific enzyme found in many pathogens. GCYH-IB is structurally distinct from the canonical type IA GCYH involved in biopterin biosynthesis in humans and animals, and thus is of interest as a potential antibacterial drug target. We report kinetic and inhibition data of Neisseria gonorrhoeae GCYH-IB and two high-resolution crystal structures of the enzyme; one in complex with the reaction intermediate analog and competitive inhibitor 8-oxoguanosine 5'-triphosphate (8-oxo-GTP), and one with a tris(hydroxymethyl)aminomethane molecule bound in the active site and mimicking another reaction intermediate. Comparison with the type IA enzyme bound to 8-oxo-GTP (guanosine 5'-triphosphate) reveals an inverted mode of binding of the inhibitor ribosyl moiety and, together with site-directed mutagenesis data, shows that the two enzymes utilize different strategies for catalysis. Notably, the inhibitor interacts with a conserved active-site Cys149, and this residue is S-nitrosylated in the structures. This is the first structural characterization of a biologically S-nitrosylated bacterial protein. Mutagenesis and biochemical analyses demonstrate that Cys149 is essential for the cyclohydrolase reaction, and S-nitrosylation maintains enzyme activity, suggesting a potential role of the S-nitrosothiol in catalysis.

Crystal structure of the archaeosine synthase QueF-like-Insights into amidino transfer and tRNA recognition by the tunnel fold.

The tunneling-fold (T-fold) structural superfamily has emerged as a versatile protein scaffold of diverse catalytic activities. This is especially evident in the pathways to the 7-deazaguanosine modified nucleosides of tRNA queuosine and archaeosine. Four members of the T-fold superfamily have been confirmed in these pathways and here we report the crystal structure of a fifth enzyme; the recently discovered amidinotransferase QueF-Like (QueF-L), responsible for the final step in the biosynthesis of archaeosine in the D-loop of tRNA in a subset of Crenarchaeota. QueF-L catalyzes the conversion of the nitrile group of the 7-cyano-7-deazaguanine (preQ0 ) base of preQ0 -modified tRNA to a formamidino group. The structure, determined in the presence of preQ0 , reveals a symmetric T-fold homodecamer of two head-to-head facing pentameric subunits, with 10 active sites at the inter-monomer interfaces. Bound preQ0 forms a stable covalent thioimide bond with a conserved active site cysteine similar to the intermediate previously observed in the nitrile reductase QueF. Despite distinct catalytic functions, phylogenetic distributions, and only 19% sequence identity, the two enzymes share a common preQ0 binding pocket, and likely a common mechanism of thioimide formation. However, due to tight twisting of its decamer, QueF-L lacks the NADPH binding site present in QueF. A large positively charged molecular surface and a docking model suggest simultaneous binding of multiple tRNA molecules and structure-specific recognition of the D-loop by a surface groove. The structure sheds light on the mechanism of nitrile amidation, and the evolution of diverse chemistries in a common fold. Proteins 2016; 85:103-116. © 2016 Wiley Periodicals, Inc.

Directed cardiomyogenesis of human pluripotent stem cells by modulating Wnt/ß-catenin and BMP signalling with small molecules.

Cardiomyocytes derived from human pluripotent stem cells (PSCs) are a potential cell source for regenerative medicine, disease modelling and drug development. However, current approaches for in vitro cardiac differentiation of human PSCs are often time-consuming, heavily depend on expensive growth factors and involve the tedious formation of embryonic bodies whose signalling pathways are difficult to precisely modulate due to their complex microenvironments. In the present study, we report a new small molecule-based differentiation approach, which significantly promoted contracting cardiomyocytes in human PSCs in a monolayer format in as little as 7 days, in contrast with most traditional differentiation methods that usually take up to 3 weeks for cardiomyogenesis. This approach consists in activation of the Wnt/ß-catenin signalling at day 0-1 with small molecule CHIR99021 (CH) followed by inhibition of bone morphogenetic protein (BMP) signalling at day 1-4 with DMH1 [termed as CH(0-1)/DMH1(1-4) treatment], a selective small molecule BMP inhibitor reported by us previously. Our study further demonstrated that the CH(0-1)/DMH1(1-4) treatment significantly promotes cardiac formation via mesoderm and mesoderm-derived cardiac progenitor cells without impacts on either endoderm or ectoderm differentiation of human PSCs. This rapid, efficient and inexpensive small molecule-based cardiomyogenic method may potentially harness the use of human PSCs in regenerative medicine as well as other applications.

Imaginación y libertad / Imagination and freedom

Daniel C. Dennett ha dedicado parte de sus reflexiones filosóficas al problema del libre albedrío. Los argumentos del autor relativos al tema se consideran compatibilistas. Es decir, asume que la libre elección en la especie humana es compatible o coexiste con la determinación. A diferencia de los argumentos convencionales, Dennett plantea su propuesta a partir del naturalismo filosófico. El texto realiza una introducción a estas ideas y esboza una comparación conceptual con el ensayo psicológico de Vygotsky dedicado a la imaginación y el arte en la infancia. Asimismo, explora en la literatura dos observaciones sugerentes del ensayo inglés de Siglo XIX en Wilde y Stevenson, que permiten concebir con mayor claridad la comparación. La imaginación y la creatividad en la infancia con el juego simbólico asociado, en definitiva, puede asimilarse como la primera experiencia de libertad en los seres humanos.

Daniel C. Dennett has devoted part of his philosophical reflections to the problem of free will. The author's arguments relating to the subject are considered compatibilist. That is, assuming that free choice in humans is supported or coexists with the determination. Unlike conventional arguments, Dennett presents his proposal from philosophical naturalism. This paper provides an introduction to these ideas and outlines a conceptual comparison with Vygotsky's psychological paper dedicated to imagination and art in childhood. It also explores two observations in the literature suggestive of nineteenth century English essay in Wilde and Stevenson, allowing more clearly conceive comparison. Imagination and creativity in childhood associated with symbolic play, ultimately, can be assimilated as the first experience of freedom in human beings.