Distinct subpopulations of DN1 thymocytes exhibit preferential γδ T lineage potential

The αβ and γδ T cell lineages both differentiate in the thymus from common uncommitted progenitors. The earliest stage of T cell development is known as CD4-CD8- double negative 1 (DN1), which has previously been shown to be a heterogenous mixture of cells. Of these, only the CD117+ fraction has been proposed to be true T cell progenitors that progress to the DN2 and DN3 thymocyte stages, at which point the development of the αβ and γδ T cell lineages diverge. However, recently, it has been shown that at least some γδ T cells may be derived from a subset of CD117- DN thymocytes. Along with other ambiguities, this suggests that T cell development may not be as straightforward as previously thought. To better understand early T cell development, particularly the heterogeneity of DN1 thymocytes, we performed a single cell RNA sequence (scRNAseq) of mouse DN and γδ thymocytes and show that the various DN stages indeed comprise a transcriptionally diverse subpopulations of cells. We also show that multiple subpopulations of DN1 thymocytes exhibit preferential development towards the γδ lineage. Furthermore, specific γδ-primed DN1 subpopulations preferentially develop into IL-17 or IFNγ-producing γδ T cells. We show that DN1 subpopulations that only give rise to IL-17-producing γδ T cells already express many of the transcription factors associated with type 17 immune cell responses, while the DN1 subpopulations that can give rise to IFNγ-producing γδ T cell already express transcription factors associated with type 1 immune cell responses

Learning from the process evaluation of a complex, pre-conception randomised controlled trial in Malaysia:The Jom Mama project

Background: Seen from a life-course perspective, pre-conception interventions are essential to reduce transmission to the next generation of obesity as a risk factor for later non-communicable diseases. The Malaysian Jom Mama project investigated the effectiveness of a combined behaviour change communication and e-health intervention in young married couples prior to first pregnancy. This paper reports on the extensive process evaluation (PE) that accompanied the Jom Mama trial.Methods: In accordance with the realistic evaluation approach, a programme theory was developed for the Jom Mama project, based on key functions selected for six PE sub-studies, namely: Recruitment; attrition; behaviour change communication (BCC); e-health (the Jom app); peer-support for community health promoters (CHPs); and contextual factors. The results of the first four sub-studies are reported here. Three cycles of data collection were conducted based on triangulation and a mixed-methods approach.Results: The findings permitted distinguishing between theory and implementation challenges in interpreting the outcome of the Jom Mama trial.1 Recruitment and attrition proved to be challenges, and although the PE allowed Jom Mama investigators to improve procedures in order to achieve a sufficient sample size, it also has implications for engaging this age group in future pre-conception interventions. PE sub-studies showed that there were challenges in applying the BCC, and that the uptake of the Jom app varied. In one way this can be seen as an indication of limited fidelity, but it also leads to questions about how best to change the communication culture within the Malaysian health care system.Conclusions: The Jom Mama PE highlighted the challenges of recruiting newly-wed couples for a pre-conception intervention. Despite thorough intervention development preparations, the PE revealed the difficulty of lifestyle behaviour change through Malaysian community health wokers who were trained on new communication strategies combined with e-health solutions, and that six intervention sessions of eight months do not constitute a sufficient dose to affect change.</p

Learning from the process evaluation of a complex, pre-conception randomised controlled trial in Malaysia:The Jom Mama project

Background: Seen from a life-course perspective, pre-conception interventions are essential to reduce transmission to the next generation of obesity as a risk factor for later non-communicable diseases. The Malaysian Jom Mama project investigated the effectiveness of a combined behaviour change communication and e-health intervention in young married couples prior to first pregnancy. This paper reports on the extensive process evaluation (PE) that accompanied the Jom Mama trial.Methods: In accordance with the realistic evaluation approach, a programme theory was developed for the Jom Mama project, based on key functions selected for six PE sub-studies, namely: Recruitment; attrition; behaviour change communication (BCC); e-health (the Jom app); peer-support for community health promoters (CHPs); and contextual factors. The results of the first four sub-studies are reported here. Three cycles of data collection were conducted based on triangulation and a mixed-methods approach.Results: The findings permitted distinguishing between theory and implementation challenges in interpreting the outcome of the Jom Mama trial.1 Recruitment and attrition proved to be challenges, and although the PE allowed Jom Mama investigators to improve procedures in order to achieve a sufficient sample size, it also has implications for engaging this age group in future pre-conception interventions. PE sub-studies showed that there were challenges in applying the BCC, and that the uptake of the Jom app varied. In one way this can be seen as an indication of limited fidelity, but it also leads to questions about how best to change the communication culture within the Malaysian health care system.Conclusions: The Jom Mama PE highlighted the challenges of recruiting newly-wed couples for a pre-conception intervention. Despite thorough intervention development preparations, the PE revealed the difficulty of lifestyle behaviour change through Malaysian community health wokers who were trained on new communication strategies combined with e-health solutions, and that six intervention sessions of eight months do not constitute a sufficient dose to affect change.</p

Learning from the process evaluation of a complex, pre-conception randomised controlled trial in Malaysia:The Jom Mama project

Background: Seen from a life-course perspective, pre-conception interventions are essential to reduce transmission to the next generation of obesity as a risk factor for later non-communicable diseases. The Malaysian Jom Mama project investigated the effectiveness of a combined behaviour change communication and e-health intervention in young married couples prior to first pregnancy. This paper reports on the extensive process evaluation (PE) that accompanied the Jom Mama trial.Methods: In accordance with the realistic evaluation approach, a programme theory was developed for the Jom Mama project, based on key functions selected for six PE sub-studies, namely: Recruitment; attrition; behaviour change communication (BCC); e-health (the Jom app); peer-support for community health promoters (CHPs); and contextual factors. The results of the first four sub-studies are reported here. Three cycles of data collection were conducted based on triangulation and a mixed-methods approach.Results: The findings permitted distinguishing between theory and implementation challenges in interpreting the outcome of the Jom Mama trial.1 Recruitment and attrition proved to be challenges, and although the PE allowed Jom Mama investigators to improve procedures in order to achieve a sufficient sample size, it also has implications for engaging this age group in future pre-conception interventions. PE sub-studies showed that there were challenges in applying the BCC, and that the uptake of the Jom app varied. In one way this can be seen as an indication of limited fidelity, but it also leads to questions about how best to change the communication culture within the Malaysian health care system.Conclusions: The Jom Mama PE highlighted the challenges of recruiting newly-wed couples for a pre-conception intervention. Despite thorough intervention development preparations, the PE revealed the difficulty of lifestyle behaviour change through Malaysian community health wokers who were trained on new communication strategies combined with e-health solutions, and that six intervention sessions of eight months do not constitute a sufficient dose to affect change.</p

Learning from the process evaluation of a complex, pre-conception randomised controlled trial in Malaysia:The Jom Mama project

Background: Seen from a life-course perspective, pre-conception interventions are essential to reduce transmission to the next generation of obesity as a risk factor for later non-communicable diseases. The Malaysian Jom Mama project investigated the effectiveness of a combined behaviour change communication and e-health intervention in young married couples prior to first pregnancy. This paper reports on the extensive process evaluation (PE) that accompanied the Jom Mama trial.Methods: In accordance with the realistic evaluation approach, a programme theory was developed for the Jom Mama project, based on key functions selected for six PE sub-studies, namely: Recruitment; attrition; behaviour change communication (BCC); e-health (the Jom app); peer-support for community health promoters (CHPs); and contextual factors. The results of the first four sub-studies are reported here. Three cycles of data collection were conducted based on triangulation and a mixed-methods approach.Results: The findings permitted distinguishing between theory and implementation challenges in interpreting the outcome of the Jom Mama trial.1 Recruitment and attrition proved to be challenges, and although the PE allowed Jom Mama investigators to improve procedures in order to achieve a sufficient sample size, it also has implications for engaging this age group in future pre-conception interventions. PE sub-studies showed that there were challenges in applying the BCC, and that the uptake of the Jom app varied. In one way this can be seen as an indication of limited fidelity, but it also leads to questions about how best to change the communication culture within the Malaysian health care system.Conclusions: The Jom Mama PE highlighted the challenges of recruiting newly-wed couples for a pre-conception intervention. Despite thorough intervention development preparations, the PE revealed the difficulty of lifestyle behaviour change through Malaysian community health wokers who were trained on new communication strategies combined with e-health solutions, and that six intervention sessions of eight months do not constitute a sufficient dose to affect change.</p

Global public policy, transnational policy communities, and their networks

Public policy has been a prisoner of the word "state." Yet, the state is reconfigured by globalization. Through "global public–private partnerships" and "transnational executive networks," new forms of authority are emerging through global and regional policy processes that coexist alongside nation-state policy processes. Accordingly, this article asks what is "global public policy"? The first part of the article identifies new public spaces where global policies occur. These spaces are multiple in character and variety and will be collectively referred to as the "global agora." The second section adapts the conventional policy cycle heuristic by conceptually stretching it to the global and regional levels to reveal the higher degree of pluralization of actors and multiple-authority structures than is the case at national levels. The third section asks: who is involved in the delivery of global public policy? The focus is on transnational policy communities. The global agora is a public space of policymaking and administration, although it is one where authority is more diffuse, decision making is dispersed and sovereignty muddled. Trapped by methodological nationalism and an intellectual agoraphobia of globalization, public policy scholars have yet to examine fully global policy processes and new managerial modes of transnational public administration

Perception of the risks and benefits of bt eggplant by Indian farmers

Several researchers—most notably Lennart Sjoberg and his colleagues—have proposed that the moral aspects of risk provide a better explanation of risk perception than the psychometric paradigm or Cultural Theory, neither of which accounts for moral concerns. This study is possibly the first to assess empirically the perception of the risks and benefits of a transgenic food crop—transgenic Bt (Bacillus thuringiensis) eggplant—by farmers in a developing country such as India. It also aims to assess if the moral aspects of risk figure in Indian farmers ’ perception of Bt eggplant and if economic benefits outweigh perceived risks. To answer the research questions, a scenario was used to elicit perceptions of Bt eggplant among 100 eggplant farmers in the state of Maharashtra in India. The findings indicate that economic benefits, safety concerns, and accountability are most salient to Indian farmers’ perception of the risks and benefits of Bt eggplant. Significantly, none of the farmers mentioned moral concerns as an issue. The findings also make clear that economic benefits outweigh perceived risks. This study concludes that economic benefits are more salient than moral concerns to Indian farmers ’ perception Bt eggplant. It also proposes that an alternative theoretical model incorporating economic benefits, safety concerns, and accountability as key variables should be developed and tested for end users in the developing world. KEY WORDS: risk perception, biotechnology, developing countries, farmers 1

Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey.

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management