How nanotechnology can be harnessed to address some of the world's most critical development problems

Background Task shifting and sharing (TS/S) involves the redistribution of health tasks within workforces and communities. Conceptual frameworks lay out the key factors, constructs, and variables involved in a given phenomenon, as well as the relationships between those factors. Though TS/S is a leading strategy to address health worker shortages and improve access to services worldwide, a conceptual framework for this approach is lacking. Methods We used an online Delphi process to engage an international panel of scholars with experience in knowledge synthesis concerning TS/S and develop a conceptual framework for TS/S. We invited 55 prospective panelists to participate in a series of questionnaires exploring the purpose of TS/S and the characteristics of contexts amenable to TS/S programmes. Panelist responses were analysed and integrated through an iterative process to achieve consensus on the elements included in the conceptual framework. Results The panel achieved consensus concerning the included concepts after three Delphi rounds among 15 panelists. The COATS Framework (Concepts and Opportunities to Advance Task Shifting and Task Sharing) offers a refined definition of TS/S and a general purpose statement to guide TS/S programmes. COATS describes that opportunities for health system improvement arising from TS/S programmes depending on the implementation context, and enumerates eight necessary conditions and important considerations for implementing TS/S programmes. Conclusion The COATS Framework offers a conceptual model for TS/S programmes. The COATS Framework is comprehensive and adaptable, and can guide refinements in policy, programme development, evaluation, and research to improve TS/S globally.

In the absence of scientific clarity about the potential health effects of occupational exposure to nanoparticles, a need exists for guidance in decisionmaking about hazards, risks, and controls. An identification of the ethical issues involved may be useful to decision makers, particularly employers, workers, investors, and health authorities. Because the goal of occupational safety and health is the prevention of disease in workers, the situations that have ethical implications that most affect workers have been identified. These situations include the a) identification and communication of hazards and risks by scientists, authorities, and employers; b) workers’ acceptance of risk; c) selection and implementation of controls; d) establishment of medical screening programs; and e) investment in toxicologic and control research. The ethical issues involve the unbiased determination of hazards and risks, nonmaleficence (doing no harm), autonomy, justice, privacy, and promoting respect for persons. As the ethical issues are identified and explored, options for decision makers can be developed. Additionally, societal deliberations about workplace risks of nanotechnologies may be enhanced by special emphasis on small businesses and adoption of a global perspective.

In the absence of scientific clarity about the potential health effects of occupational exposure to nanoparticles, a need exists for guidance in decision making about hazards, risks, and controls. An identification of the ethical issues involved may be useful to decision makers, particularly employers, workers, investors, and health authorities. Because the goal of occupational safety and health is the prevention of disease in workers, the situations that have ethical implications that most affect workers have been identified. These situations include the a) identification and communication of hazards and risks by scientists, authorities, and employers; b) workers' acceptance of risk; c) selection and implementation of controls; d) establishment of medical screening programs; and e) investment in toxicologic and control research. The ethical issues involve the unbiased determination of hazards and risks, nonmaleficence (doing no harm), autonomy, justice, privacy, and promoting respect for persons. As the ethical issues are identified and explored, options for decision makers can be developed. Additionally, societal deliberations about workplace risks of nanotechnologies may be enhanced by special emphasis on small businesses and adoption of a global perspective.

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The Ras family of small Guanosine Triphosphate (GTP)-binding proteins (G proteins) represents one of the main components of intracellular signal transduction required for normal cardiac growth, but is also critically involved in the development of cardiac hypertrophy and heart failure. The present review provides an update on the role of the H-, K- and N-Ras genes and their related pathways in cardiac diseases. We focus on cardiac hypertrophy and heart failure, where Ras has been studied the most. We also review other cardiac diseases, like genetic disorders related to Ras. The scope of the review extends from fundamental concepts to therapeutic applications. Although the three Ras genes have a nearly identical primary structure, there are important functional differences between them: H-Ras mainly regulates cardiomyocyte size, whereas K-Ras regulates cardiomyocyte proliferation. N-Ras is the least studied in cardiac cells and is less associated to cardiac defects. Clinically, oncogenic H-Ras causes Costello syndrome and facio-cutaneous-skeletal syndromes with hypertrophic cardiomyopathy and arrhythmias. On the other hand, oncogenic K-Ras and alterations of other genes of the Ras-Mitogen-Activated Protein Kinase (MAPK) pathway, like Raf, cause Noonan syndrome and cardio-facio-cutaneous syndromes characterized by cardiac hypertrophy and septal defects. We further review the modulation by Ras of key signaling pathways in the cardiomyocyte, including: (i) the classical Ras-Raf-MAPK pathway, which leads to a more physiological form of cardiac hypertrophy; as well as other pathways associated with pathological cardiac hypertrophy, like (ii) The SAPK (stress activated protein kinase) pathways p38 and JNK; and (iii) The alternative pathway Raf-Calcineurin-Nuclear Factor of Activated T cells (NFAT). Genetic alterations of Ras isoforms or of genes in the Ras-MAPK pathway result in Ras-opathies, conditions frequently associated with cardiac hypertrophy or septal defects among other cardiac diseases. Several studies underline the potential role of H- and K-Ras as a hinge between physiological and pathological cardiac hypertrophy, and as potential therapeutic targets in cardiac hypertrophy and failure. Graphic abstract

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Despite their burden and high prevalence, mental health disorders of children and adolescents remain neglected in many parts of the world. In developing countries, where half of the population is younger than 18 years old, one of every five children and adolescents is estimated to suffer from a mental health disorder. It is then essential to detect these conditions through screening in a timely and accurate manner. But such screening is fraught with considerable ethical, social, and cultural challenges. This study systematically identifies, for the first time, these challenges, along with potential solutions to address them. We report on the results of an international multi-and inter-disciplinary three-round Delphi survey completed by 135 mental health experts from 37 countries. We asked these experts to identify and rank the main ethical, social, and cultural challenges of screening for child and adolescent mental health problems in developing nations, and to propose solutions for each challenge. Thirty-nine significant challenges emerged around eight themes, along with 32 potential solutions organized into seven themes. There was a high degree of consensus among the experts, but a few interesting disagreements arose between members of the panel from high-income countries and those from low-and middle-income nations. The panelists overwhelmingly supported mental health screening for children and adolescents. They recommended ensuring local acceptance and support for screening prior to program initiation, along with careful and comprehensive protection of human rights; integrating screening procedures into primary care; designing and implementing culturally appropriate screening tools, programs, and follow-up; securing longterm funding; expanding capacity building; and task-shifting screening to local non-specialists. These recommendations can serve as a guide for policy and decision-making, resource allocation, and international cooperation. They also offer a novel approach to