Sharing What Works Through South-South Cooperation: The Case of the Risk Reduction Management Centre Replication Project

The Risk Reduction Management Centre (RRMC) Replication Project, an initiative of the United Nations Development Program (UNDP), aims to take a Cuban best practice in disaster risk reduction and adapt it to the local context of five other Caribbean countries. This project differs from most development projects in that the individuals and institutions providing the assistance (in this case technical training and know-how) are themselves from a developing country (Cuba). This model, wherein developing countries provide resources, information, and training to other developing countries, is known as South-South Cooperation (SSC). This capstone uses the case of the RRMC Replication Project to offer recommendations for SSC. The questions that it specifically aims to address are: What are the advantages and disadvantages of technical SSC? How do the general advantages and disadvantages found in the literature apply to the RRMC Replication project? Are there additional advantages and disadvantages that can be drawn out from the RRMC Replication Project? And how can the RRMC Replication Project best use the advantages of SSC, and address its disadvantages, for the remainder of the project (scheduled to conclude in December 2013)? Using the case study methodology, this capstone assesses the RRMC Replication Project through a review of primary and secondary documents and video footage, reflections on the author’s personal experience as a UNDP intern, and in-depth interviews with individuals involved in the Project. The study finds that using the lens of the RRMC Replication Project many of the advantages of SSC are revealed, including the ability to share proven solutions among similar countries that results from the similar contexts of receiving and providing countries; the emphasis on adapting projects to the local context of the receiving country; the value of having an extensive and two-way exchange of knowledge that benefits all parties involved and leads to increased regional solidarity; the empowering effect that SSC can have on both receiving and providing countries; the humility and respect for national sovereignty shown by the providing country; and the lower costs of SSC–all leading to more efficient and more sustainable development. Disadvantages and challenges of SSC seen in the RRMC Replication Project include lack of capacity for the providing country to share the information effectively and for the receiving country to take on the information effectively, the assumption that because a model works in one place it will automatically work in a neighboring country, and not being able to avoid issues that all development projects seem to have. This research shows in practical terms the strengths and challenges of SSC technical exchange and explains why UNDP is in a unique position to advocate and facilitate such exchanges. The RRMC Replication Project has facilitated the meaningful exchange of knowledge about disaster risk reduction among six countries and among multiple government agencies, professional institutions, and individuals, leading to increased understanding and increased preparedness across the Caribbean. The author concludes that the RRMC Replication Project demonstrates the value of SSC and provides an example of the possibility of bringing the best of the North-South and South-South models together to promote truly sustainable development on a regional level

Impact of a Reduced Nicotine Standard on Young Adult Appeal for Menthol and Non-Menthol Cigarettes

Introduction The Food and Drug Administration (FDA) announced its intention to reduce the nicotine content in cigarettes as a strategy to promote cessation and reduce smoking-related harm. A low nicotine product standard will apply to all cigarettes on the market, including menthol cigarettes. In December 2021, the FDA approved a modified risk tobacco product application for menthol and non-menthol flavoured very low nicotine cigarettes (VLNC) from the 22nd Century Group. Notably, experimentation with menthol cigarettes is linked to smoking progression, as well as greater nicotine dependence relative to non-menthol cigarette use. If menthol VLNCs are perceived as more appealing than non-menthol VLNCs, this would indicate that some aspect of menthol may maintain smoking even in the absence of nicotine and FDA’s regulatory authority to ban or restrict the sale of menthol cigarettes should apply to reduced nicotine content of cigarettes. In April 2022, the FDA announced proposed rulemaking to prohibit menthol cigarettes, however it is unclear if a menthol prohibition would apply to VLNCs. Methods and analysis This study will recruit 172 young adult menthol smokers (with a specific subsample of n=40 sexual and gender minority young adults) and measure appeal for smoking experimental menthol and non-menthol VLNCs, and the impact of proposed product standards on tobacco product purchasing behaviour using an Experimental Tobacco Marketplace. Appeal across product standards will be assessed in a controlled laboratory and using ecological momentary assessment. Ethics and dissemination The protocol was approved by the University of Oklahoma Health Sciences Center Institutional Review Board (#11865). Findings will examine the effects of a reduced nicotine standard and a menthol ban on young adult smoking and will be disseminated through peer-reviewed journal articles and presentations at scientific conferences. Trial registration number NCT04340947

Actinin BioID reveals sarcomere crosstalk with oxidative metabolism through interactions with IGF2BP2.

Actinins are strain-sensing actin cross-linkers that are ubiquitously expressed and harbor mutations in human diseases. We utilize CRISPR, pluripotent stem cells, and BioID to study actinin interactomes in human cardiomyocytes. We identify 324 actinin proximity partners, including those that are dependent on sarcomere assembly. We confirm 19 known interactors and identify a network of RNA-binding proteins, including those with RNA localization functions. In vivo and biochemical interaction studies support that IGF2BP2 localizes electron transport chain transcripts to actinin neighborhoods through interactions between its K homology (KH) domain and actinin\u27s rod domain. We combine alanine scanning mutagenesis and metabolic assays to disrupt and functionally interrogate actinin-IGF2BP2 interactions, which reveal an essential role in metabolic responses to pathological sarcomere activation using a hypertrophic cardiomyopathy model. This study expands our functional knowledge of actinin, uncovers sarcomere interaction partners, and reveals sarcomere crosstalk with IGF2BP2 for metabolic adaptation relevant to human disease

A Contraction Stress Model of Hypertrophic Cardiomyopathy due to Sarcomere Mutations.

Thick-filament sarcomere mutations are a common cause of hypertrophic cardiomyopathy (HCM), a disorder of heart muscle thickening associated with sudden cardiac death and heart failure, with unclear mechanisms. We engineered four isogenic induced pluripotent stem cell (iPSC) models of β-myosin heavy chain and myosin-binding protein C3 mutations, and studied iPSC-derived cardiomyocytes in cardiac microtissue assays that resemble cardiac architecture and biomechanics. All HCM mutations resulted in hypercontractility with prolonged relaxation kinetics in proportion to mutation pathogenicity, but not changes in calcium handling. RNA sequencing and expression studies of HCM models identified p53 activation, oxidative stress, and cytotoxicity induced by metabolic stress that can be reversed by p53 genetic ablation. Our findings implicate hypercontractility as a direct consequence of thick-filament mutations, irrespective of mutation localization, and the p53 pathway as a molecular marker of contraction stress and candidate therapeutic target for HCM patients

Group elastic symmetries common to continuum and discrete defective crystals

The Lie group structure of crystals which have uniform continuous distributions of dislocations allows one to construct associated discrete structures—these are discrete subgroups of the corresponding Lie group, just as the perfect lattices of crystallography are discrete subgroups of R 3 , with addition as group operation. We consider whether or not the symmetries of these discrete subgroups extend to symmetries of (particular) ambient Lie groups. It turns out that those symmetries which correspond to automorphisms of the discrete structures do extend to (continuous) symmetries of the ambient Lie group (just as the symmetries of a perfect lattice may be embedded in ‘homogeneous elastic’ deformations). Other types of symmetry must be regarded as ‘inelastic’. We show, following Kamber and Tondeur, that the corresponding continuous automorphisms preserve the Cartan torsion, and we characterize the discrete automorphisms by a commutativity condition, (6.14), that relates (via the matrix exponential) to the dislocation density tensor. This shows that periodicity properties of corresponding energy densities are determined by the dislocation density

A classification of the symmetries of uniform discrete defective crystals

Crystals which have a uniform distribution of defects are endowed with a Lie group description which allows one to construct an associated discrete structure. These structures are in fact the discrete subgroups of the ambient Lie group. The geometrical symmetries of these structures can be computed in terms of the changes of generators of the discrete subgroup which preserve the discrete set of points. Here a classification of the symmetries for the discrete subgroups of a particular class of three-dimensional solvable Lie group is presented. It is a fact that there are only three mathematically distinct types of Lie groups which model uniform defective crystals, and the calculations given here complete the discussion of the symmetries of the corresponding discrete structures. We show that those symmetries corresponding to automorphisms of the discrete subgroups extend uniquely to symmetries of the ambient Lie group and we regard these symmetries as (restrictions of) elastic deformations of the continuous defective crystal. Other symmetries of the discrete structures are classified as ‘inelastic’ symmetries

Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.

Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies

Resilient Pedagogy: Practical Teaching Strategies to Overcome Distance, Disruption, and Distraction

Resilient Pedagogy offers a comprehensive collection on the topics and issues surrounding resilient pedagogy framed in the context of the COVID-19 pandemic and the social justice movements that have swept the globe. As a collection, Resilient Pedagogy is a multi-disciplinary and multi-perspective response to actions taken in different classrooms, across different institution types, and from individuals in different institutional roles with the purpose of allowing readers to explore the topics to improve their own teaching practice and support their own students through distance, disruption, and distraction

Discourses of student orientation to medical education programs

Background: Although medical students’ initial orientation is an important point of transition in medical education, there is a paucity of literature on the subject and major variations in the ways that different institutions orient incoming medical students to their programs. Methods: We conducted a discourse analysis of medical education orientation in the literature and on data from a survey of peer institutions’ approaches to orientation. Results: These two discourses of orientation had clear similarities, in particular, the critical role of ceremony and symbols, and the focus on developing professionalism and physician identities. There were also differences between them, in particular, in the way that the discourse in the literature focused on the symbolic and professional aspects of orientation; something we have called ‘cultural orientation’. Meanwhile, those who were responsible for orientation in their own institutions tended to focus on the practical and social dimensions. Conclusion: By examining how orientation has been described and discussed, we identify three domains of orientation: cultural, social, and practical. These domains are relatively distinct in terms of the activities associated with them, and in terms of who is involved in organizing and running these activities. We also describe orientation as a liminal activity system on the threshold of medical school where incoming students initially cross into the profession. Interestingly, this state of ambiguity also extends to the scholarship of orientation with only some of its aspects attracting formal enquiry, even though there is a growing interest in transitions in medical education as a whole. We hope, therefore, that this study can help to legitimize enquiry into orientation in all its forms and that it can begin to situate the role of orientation more firmly within the firmament of medical education practice and research