Cardiac Progenitor Cells from Stem Cells: Learning from Genetics and Biomaterials

Cardiac Progenitor Cells (CPCs) show great potential as a cell resource for restoring cardiac function in patients affected by heart disease or heart failure. CPCs are proliferative and committed to cardiac fate, capable of generating cells of all the cardiac lineages. These cells offer a significant shift in paradigm over the use of human induced pluripotent stem cell (iPSC)-derived cardiomyocytes owing to the latter's inability to recapitulate mature features of a native myocardium, limiting their translational applications. The iPSCs and direct reprogramming of somatic cells have been attempted to produce CPCs and, in this process, a variety of chemical and/or genetic factors have been evaluated for their ability to generate, expand, and maintain CPCs in vitro. However, the precise stoichiometry and spatiotemporal activity of these factors and the genetic interplay during embryonic CPC development remain challenging to reproduce in culture, in terms of efficiency, numbers, and translational potential. Recent advances in biomaterials to mimic the native cardiac microenvironment have shown promise to influence CPC regenerative functions, while being capable of integrating with host tissue. This review highlights recent developments and limitations in the generation and use of CPCs from stem cells, and the trends that influence the direction of research to promote better application of CPCs

Endogenous Technological Change in Energy Systems Models: Synthesis of Experience with ERIS, MARKAL, and MESSAGE

Technological change is widely recognised as a key factor in economic progress, as it enhances the productivity of factor inputs. In recent years also the notion has developed that targeted technological development is a main means to reconcile economic ambitions with ecological considerations. This raises the issue that assessments of future trajectories of for example en-ergy systems should take into account context-specific technological progress. Rather than tak-ing characteristics of existing and emerging technologies as a given, their development should be a function of dedicated Research, Development and Demonstration (RD&D) and market de-ployment under varying external conditions. Endogenous technological learning has recently shown to be a very promising new feature in energy system models. A learning, or experience curve, describes the specific (investment) cost as a function of the cumulative capacity for a given technology. It reflects the fact that tech-nologies may experience declining costs as a result of its increasing adoption into the society due to the accumulation of knowledge through, among others, processes of learning-by-doing and learning-by-using. This report synthesises the results and findings from experiments with endogenous technologi-cal learning, as reported separately within the EU TEEM project. These experiments have been carried out by three TEEM partners using three models: ERIS (PSI), MARKAL (ECN and PSI), and MESSAGE (IIASA). The main objectives of this synthesis are: to derive common methodo-logical insights; to indicate and assess benefits of the new feature, but also its limitations and issues to solve; and to recommend further research to solve the main issues. This synthesis shows that all model applications are examples of successful first experiments to incorporate the learning-by-doing concept in energy system models. Incorporating the learning-by-doing concept makes an important difference. The experiments demonstrate and quantify the benefits of investing early in emerging technologies that are not competitive at the moment of their deployment. They also show that the long-term impact of policy instruments, such as CO2 taxes or emission limits and RD&D instruments, on technological development can be assessed adequately with models including technology learning. Adopting the concept of endogenous learning, several types of RD&D interventions can be addressed that aim at accelerating the market penetration of new technologies. The directions into which such interventions might lead have been illustrated in some of the experiments. However, quantitative relationships between R&D policy and learning data parameters are still unknow

Socioeconomic and environmental determinants of adolescent asthma in urban Latin America: an ecological analysis

The prevalence of asthma is high in urban areas of many Latin-American countries where societies show high levels of inequality and different levels of development. This study aimed to examine the relationship between asthma symptoms prevalence in adolescents living in Latin American urban centers and socioeconomic and environmental determinants measured at the ecological level. Asthma prevalence symptoms were obtained from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III. A hierarchical conceptual framework was defined and the explanatory variables were organized in three levels: distal, intermediate, proximal. Linear regression models weighed by sample size were undertaken between asthma prevalence and the selected variables. Asthma prevalence was positively associated with Gini index, water supply and homicide rate, and inversely associated with the Human Development Index, crowding and adequate sanitation. This study provides evidence of the potential influence of poverty and social inequalities on current wheezing in adolescents in a complex social context like Latin America.A prevalência da asma é alta nas áreas urbanas da América Latina, onde as sociedades exibem altos níveis de desigualdade e diferente grau de desenvolvimento. O objetivo é examinar a relação entre a prevalência de sintomas asmáticos em adolescentes de centros urbanos da América Latina e determinantes socioeconômicos e ambientais medidos no nível ecológico. A prevalência de sintomas asmáticos foi obtida do International Study of Asthma and Allergies in Childhood (ISAAC), fase III. Foi definido um modelo conceitual hierárquico. As variáveis explicativas foram organizadas em três níveis: distal, intermediário, proximal. Ajustaram-se modelos de regressão lineal ponderados pelo tamanho amostral entre prevalência de sintomas asmáticos e variáveis selecionadas. A prevalência da asma foi associada positivamente com índice de Gini, índice de desenvolvimento humano, subministro de água potável, e inversamente com aglomeração e saneamento. Em conclusão, este estudo ecológico fornece evidência da influência da pobreza e da desigualdade social sobre os sintomas asmáticos em adolescentes em um contexto social complexo como o da América Latina

Geodesic stability, Lyapunov exponents and quasinormal modes

Geodesic motion determines important features of spacetimes. Null unstable geodesics are closely related to the appearance of compact objects to external observers and have been associated with the characteristic modes of black holes. By computing the Lyapunov exponent, which is the inverse of the instability timescale associated with this geodesic motion, we show that, in the eikonal limit, quasinormal modes of black holes in any dimensions are determined by the parameters of the circular null geodesics. This result is independent of the field equations and only assumes a stationary, spherically symmetric and asymptotically flat line element, but it does not seem to be easily extendable to anti-de Sitter spacetimes. We further show that (i) in spacetime dimensions greater than four, equatorial circular timelike geodesics in a Myers-Perry black hole background are unstable, and (ii) the instability timescale of equatorial null geodesics in Myers-Perry spacetimes has a local minimum for spacetimes of dimension d > 5.Comment: 13 pages, 2 Figs, RevTex4. v2: Minor corrections. v3: more minor correction

Domains and processes for institutionalizing evidence-informed health policy-making: a critical interpretive synthesis

BACKGROUND: While calls for institutionalization of evidence-informed policy-making (EIP) have become stronger in recent years, there is a paucity of methods that governments and organizational knowledge brokers can use to sustain and integrate EIP as part of mainstream health policy-making. The objective of this paper was to conduct a knowledge synthesis of the published and grey literatures to develop a theoretical framework with the key features of EIP institutionalization. METHODS: We applied a critical interpretive synthesis (CIS) that allowed for a systematic, yet iterative and dynamic analysis of heterogeneous bodies of literature to develop an explanatory framework for EIP institutionalization. We used a "compass" question to create a detailed search strategy and conducted electronic searches to identify papers based on their potential relevance to EIP institutionalization. Papers were screened and extracted independently and in duplicate. A constant comparative method was applied to develop a framework on EIP institutionalization. The CIS was triangulated with the findings of stakeholder dialogues that involved civil servants, policy-makers and researchers. RESULTS: We identified 3001 references, of which 88 papers met our eligibility criteria. This CIS resulted in a definition of EIP institutionalization as the "process and outcome of (re-)creating, maintaining and reinforcing norms, regulations, and standard practices that, based on collective meaning and values, actions as well as endowment of resources, allow evidence to become-over time-a legitimate and taken-for-granted part of health policy-making". The resulting theoretical framework comprised six key domains of EIP institutionalization that capture both structure and agency: (1) governance; (2) standards and routinized processes; (3) partnership, collective action and support; (4) leadership and commitment; (5) resources; and (6) culture. Furthermore, EIP institutionalization is being achieved through five overlapping stages: (i) precipitating events; (ii) de-institutionalization; (iii) semi-institutionalization (comprising theorization and diffusion); (iv) (re)-institutionalization; and (v) renewed de-institutionalization processes. CONCLUSIONS: This CIS advances the theoretical and conceptual discussions on EIP institutionalization, and provides new insights into an evidence-informed framework for initiating, strengthening and/or assessing efforts to institutionalize EIP

The Burkholderia Cenocepacia OmpA-Like Protein BCAL2958: Identification, Characterization, and Detection of Anti-BCAL2958 Antibodies in Serum from B. Cepacia Complex-Infected Cystic Fibrosis Patients

Respiratory infections by bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among cystic fibrosis patients, highlighting the need for novel therapeutic strategies. In the present work we have studied the B. cenocepacia protein BCAL2958, a member of the OmpA-like family of proteins, demonstrated as highly immunogenic in other pathogens and capable of eliciting strong host immune responses. The encoding gene was cloned and the protein, produced as a 6× His-tagged derivative, was used to produce polyclonal antibodies. Bioinformatics analyses led to the identification of sequences encoding proteins with a similarity higher than 96 % to BCAL2958 in all the publicly available Bcc genomes. Furthermore, using the antibody it was experimentally demonstrated that this protein is produced by all the 12 analyzed strains from 7 Bcc species. In addition, results are also presented showing the presence of anti-BCAL2958 antibodies in sera from cystic fibrosis patients with a clinical record of respiratory infection by Bcc, and the ability of the purified protein to in vitro stimulate neutrophils. The widespread production of the protein by Bcc members, together with its ability to stimulate the immune system and the detection of circulating antibodies in patients with a documented record of Bcc infection strongly suggest that the protein is a potential candidate for usage in preventive therapies of infections by Bcc