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From Evidence to Scale: Implementation Science and Simulation Modeling to Transform HIV-Hypertension Care Integration
Project Summary As HIV programs mature, cardiovascular disease (CVD) is becoming a leading contributor to morbidity and mortality. Integration of HIV and CVD prevention, with a focus on hypertension–the most prevalent and impactful modifiable CVD risk factor, presents an opportunity to build more robust primary health systems that improve health outcomes and advance health system sustainability–a key priority for the U.S. PEPFAR program. Using an expanded version of the HIV Synthesis microsimulation model—which incorporates hypertension and CVD outcomes—and data from the NHLBI-funded HLB-SIMPLe consortium’s cluster randomized trials in six African countries, we will evaluate the health effects, cost-effectiveness, and scalability of implementation strategies to promote HIV-hypertension integration to improve health outcomes for people with and without HIV under a range of health system constraints. Our first aim is to develop and validate an additional layer to HIV Synthesis model that accounts for health system constraints and implementation strategies for integration of HIV and hypertension care. This will include parameterization using data from the WHO Health System Building Blocks framework and empiric data from trials in the HLB-SIMPLe consortium. Our second aim is to evaluate the health effects and cost-effectiveness of implementation strategies for HIV-hypertension integration to identify the most effective and scalable approaches for settings with varying health system constraints representative of conditions in west, east, and southern Africa. Analyses will include scenarios targeting people with HIV and scaling up to the broader population. Our third aim focuses on engaging policymakers and program managers to promote uptake of findings through dissemination workshops and interactive modeling tools, with tailored model outputs to specific health system contexts. Using qualitative interviews with policymakers, we will use the Weiss schema for conceptualizing research utilization to assess model impact on decision-making. We will use the Translational Science Benefits Model, to capture, classify and conceptualize the clinical, policy, economic, and operational impacts and identify barriers and facilitators to use in country programs focused on HIV, hypertension, and related NCDs. The overarching project goal is to inform evidence-based, cost-effective implementation strategies for integrating NCD care into HIV platforms, improving population health outcomes in Africa and advancing implementation science through generalizable knowledge about the intersection of implementation strategies, health system strength, and service integration.
SUPPORT SERVICES FOR THE PREVENTION AND TREATMENT THROUGH A COMPREHENSIVE CARE CONTINUUM FOR HIV-AFFECTED ADOLESCENTS IN RESOURCE CONSTRAINED SETTINGS IMPLEMENTATION SCIENCE NETWORK
Support Services for the Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings Implementation Science Network (PATC3H-IN) (UG1/UM2) Program The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) requires support for logistical and operational coordination, website and communication management, analytic and data management, infrastructure for emerging research, regulatory, and monitoring of research activities for the Prevention and Treatment through a Comprehensive Care Continuum for HIV-affected Adolescents in Resource Constrained Settings Implementation Science Network (PATC3H-IN) (UG1/UM2) Program. The NICHD and partner NIH Institutes anticipate funding 8 PATC3H-IN UG1 awards in Asia and throughout sub-Saharan Africa in 2023 through a cooperative agreement mechanism for interventions of high public health significance: The prevention of new HIV infections among adolescents at risk, and the identification of, linkage to and retention in care of, and long-term viral suppression among youth living with HIV in low-to-middle income countries with high HIV burden. The PATC3H-IN network will expand and/or improve on successes achieved by its predecessor, PATC3H, to new geographic settings and/or risk populations and stimulate much needed implementation science (IS) research in the prevention of new HIV infections among adolescents at risk and the identification of, and linkage and retention to care of and long-term viral suppression among youth living with HIV in low-to-middle income countries (LMICs). PATC3H-IN will establish a network of investigators with multidisciplinary expertise on the youth-specific PHCC and in IS research, whose mission will be to evaluate promising prevention innovations contextually and developmentally tailored for HIV uninfected at-risk youth, and treatment and care interventions for youth living with HIV which have demonstrated efficacy and/or effectiveness in adolescent or adult populations and to translate them into public health practices. The structure of PATC3H-IN will consist of multiple interdependent functional components: (1) Five Clinical Research Centers (CRC) awarded through the UG1 grant mechanism; (2) one Implementation Science Coordinating Center (ISCC) to be awarded through a UM2 grant mechanism in 2024; and (3) a Scientific Leadership Committee (SLC). The CRCs will conduct clinical research and clinical trials, including implementation, effectiveness, and hybrid implementation-effectiveness studies at their 8-or more participating Clinical Research Performance Sites (CRPS). The ISCC will establish infrastructure to support research education and capacity building across PATC3H-IN, as well as infrastructure for stakeholder engagement in and dissemination of findings from PATC3H-IN and advanced statistical modeling support across PATC3H-IN. The ISCC will also provide infrastructure for conducting foundational research to support the work of clinical sites, including possible modeling studies and translation projects, as well as national surveys, and/or systematic collection and analysis of relevant policies and laws. Lastly, the SLC will be responsible for PATC3H-IN governance, oversight, and coordination, and will develop and implement the network research agenda, convening working groups as needed, prioritizing emerging research projects, efficiently managing the development of clinical protocols, implementing and completing clinical trials, and ensuring timely publication and communication of results.
Targeting subtype specification as a driver of PDAC health disparities
PROJECT SUMMARY Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease that is refractory to current treatment strategies due in part to adaptive mechanisms of chemoresistance. Racial health disparities also confound the treatment and care of these patients. Blacks (people with African genetic ancestry) have significantly higher incidence rates of PDAC and decreased survival times compared to Caucasians (White genetic ancestry) even after socioeconomic status and tumor stages are controlled. Therefore, it is possible different racial groups exhibit unique molecular characteristics in PDAC tumors that contribute to these health disparities. The unique molecular characteristics that distinguish PDAC tumors between racial groups exhibiting disparities have the potential to identify new therapeutic targets. In a previous study, we identified 4 distinct subtypes of PDAC (Metabolic, Progenitor-like, Proliferative, and Inflammatory) that can be distinguished using multivariate analysis of quantitative proteomic data. While these PDAC subtypes are predictive of therapeutic response, this has not yet been analyzed in disparity factor balanced studies. We have examined the proteomes of primary PDAC tumors using quantitative mass spectrometry and identified unique protein signatures for Blacks and Whites. PDAC tumors from Black patients display features consistent with the Inflammatory subtype of PDAC, which is characterized by an inflamed microenvironment expressing complement proteins that can promote resistance to chemotherapy. Therefore, it is possible that race influences subtype and Blacks could preferentially develop the more aggressive and treatment refractory Inflammatory subtype. Strategies are needed to modulate subtype to improve response to chemotherapy. Toward this goal, our proteomic analysis identified polycomb repressor complex 1 (PRC1) protein RNF2 as being upregulated in PDACs from Blacks compared to Whites. We have also discovered that RNF2 regulates mRNA expression of the PDAC subtype specification factor GATA6 and inhibiting RNF2 promotes a molecular shift toward the more chemosensitive Classical subtype of PDAC. Therapeutic targeting can be achieved with Tazemetostat that inhibits the upstream PRC2 to prevent RNF2 binding the GATA6 promoter leading to its increased expression. Additionally, the Inflammatory subtype characterized by innate immune complement protein activation could be targeted with another FDA approved drug, Avacopan, which has not previously been studied in PDAC. Therefore, the Specific Aims of this proposal are designed to: 1) Evaluate the extent to which Tazemetostat treatment impacts chemotherapy-induced subtype plasticity in patient derived organoids; and 2) To determine the extent to which strategies targeting pathways associated with PDAC disparities affect progression and subtype characteristics in vivo. The successful completion of these aims has the potential to be moved quickly into phase I clinical trials since both Tazemetostat and Avacopan are FDA approved drugs. Furthermore, if successful, this project has the potential to mitigate health disparities in PDAC and broadly improve patient outcomes by implementing new precision interventions. The mouse models we propose faithfully recapitulate pancreatic cancer's clinical syndrome, histopathology and molecular properties, including the often-unique features of the stromal and immune responses that constitute the complex desmoplasia of this disease, which cannot be addressed using in vitro model systems
There’s more to timing than time: P-centers, beat bins and groove in musical microrhythm
How does the dynamic shape of a sound affect its perceived microtiming? In the TIME project, we studied basic aspects of musical microrhythm, exploring both stimulus features and the participants’ enculturated expertise via perception experiments, observational studies of how musicians produce particular microrhythms, and ethnographic studies of musicians’ descriptions of microrhythm. Collectively, we show that altering the microstructure of a sound (“what” the sound is) changes its perceived temporal location (“when” it occurs). Specifically, there are systematic effects of core acoustic factors (duration, attack) on perceived timing. Microrhythmic features in longer and more complex sounds can also give rise to different perceptions of the same sound. Our results shed light on conflicting results regarding the effect of microtiming on the “grooviness” of a rhythm.
A Toolkit to Succeed in Neuroscience in Africa - an IBRO-ALBA-WWN-SANS Webinar
Following up on last year's webinar - What it takes to succeed as a neuroscientist in Africa, this panel discussion aims at creating a guide to the skill set needed to be a neuroscientist in the African continent. Chairs and panelists will illustrate different areas of expertise as part of the "Toolkit" by matching them to real life experience and solutions that they had to find while building their career as scientists.
ALBA-WWN Webinar: What it takes to succeed as a neuroscientist in Africa
In this webinar, the ALBA Network & World Women in Neuroscience partner to address equity, inclusion & diversity issues across the Sub-Saharan African neuroscience community. The panel discussion will explore the challenges and biases faced by African neuroscientists while establishing their careers - focusing on a lack of mentoring and networking but also on the difficulties to raise funding - as well as display the strengths present in the region, which can be exploited to find solutions. Registration is free but required: https://www.alba.network/alba-wwn-webinar-africa
Using opsin genes to see through the eyes of a fish
Many animals are highly visual. They view their world through photoreceptors sensitive to different wavelengths of light. Animal survival and optimal behavioral performance may select for varying photoreceptor sensitivities depending on animal habitat or visual tasks. Our goal is to understand what drives visual diversity from both an evolutionary and molecular perspective. The group of more than 2000 cichlid fish species are an ideal system for examining such diversity. Cichlid are a colorful group of fresh water fishes. They have undergone adaptive radiation throughout Africa and the new world and occur in rivers and lakes that vary in water clarity. They are also behaviorally complex, having diverse behaviors for foraging, mate choice and even parental care. As a result, cichlids have highly diverse visual systems with cone sensitivities shifting by 30-90 nm between species. Although this group has seven cone opsin genes, individual species differ in which subset of the cone opsins they express. Some species show developmental shifts in opsin expression, switching from shorter to longer wavelength opsins through ontogeny. Other species modify that developmental program to express just one of the sets, causing the large sensitivity differences. Cichlids are therefore natural mutants for opsin expression. We have used cichlid diversity to explore the relationship between visual sensitivities and ecology. We have also exploited the genomic power of the cichlid system to identify genes and mutations that cause opsin expression shifts. Ultimately, our goal is to learn how different cichlid species see the world and whether differences matter. Behavioral experiments suggest they do indeed use color vision to survive and thrive. Cichlids therefore are a unique model for exploring how visual systems evolve in a changing world.
Portable neuroscience: using devices and apps for diagnosis and treatment of neurological disease
Scientists work in laboratories; comfortable spaces which we equip and configure to be ideal for our needs. The scientific paradigm has been adopted by clinicians, who run diagnostic tests and treatments in fully equipped hospital facilities. Yet advances in technology mean that that increasingly many functions of a laboratory can be compressed into miniature devices, or even into a smartphone app. This has the potential to be transformative for healthcare in developing nations, allowing complex tests and interventions to be made available in every village. In this talk, I will give two examples of this approach from my recent work. In the field of stroke rehabilitation, I will present basic research which we have conducted in animals over the last decade. This reveals new ways to intervene and strengthen surviving pathways, which can be deployed in cheap electronic devices to enhance functional recovery. In degenerative disease, we have used Bayesian statistical methods to improve an algorithm to measure how rapidly a subject can stop an action. We then implemented this on a portable device and on a smartphone app. The measurement obtained can act as a useful screen for Parkinson’s Disease. I conclude with an outlook for the future of this approach, and an invitation to those who would be interesting in collaborating in rolling it out to in African settings.
Kamala Harris and the Construction of Complex Ethnolinguistic Political Identity
Over the past 50 years, sociolinguistic studies on black Americans have expanded in both theoretical and technical scope, and newer research has moved beyond seeing speakers, especially black speakers, as a monolithic sociolinguistic community (Wolfram 2007, Blake 2014). Yet there remains a dearth of critical work on complex identities existing within black American communities as well as how these identities are reflected and perceived in linguistic practice. At the same time, linguists have begun to take greater interest in the ways in which public figures, such as politicians, may illuminate the wider social meaning of specific linguistic variables. In this talk, I will present results from analyses of multiple aspects of ethnolinguistic variation in the speech of Vice President Kamala Harris during the 2019-2020 Democratic Party Primary debates. Together, these results show how VP Harris expertly employs both enregistered and subtle linguistic variables, including aspects of African American Language morphosyntax, vowels, and intonational phonology in the construction and performance of a highly specific sociolinguistic identity that reflects her unique positions politically, socially, and racially. The results of this study expand our knowledge about how the complexities of speaker identity are reflected in sociolinguistic variation, as well as press on the boundaries of what we know about how speakers in the public sphere use variation to reflect both who they are and who we want them to be.
Neurotoxicity is a major health problem in Africa: focus on Parkinson's / Parkinsonism
Parkinson's disease (PD) is the second most present neurodegenerative disease in the world after Alzheimer's. It is due to the progressive and irreversible loss of dopaminergic neurons of the substantia nigra Pars Compacta. Alpha synuclein deposits and the appearance of Lewi bodies are systematically associated with it. PD is characterized by four cardinal motor symptoms: bradykinesia / akinesia, rigidity, postural instability and tremors at rest. These symptoms appear when 80% of the dopaminergic endings disappear in the striatum. According to Braak's theory, non-motor symptoms appear much earlier and this is particularly the case with anxiety, depression, anhedonia, and sleep disturbances. In 90 to 95% of cases, the causes of the appearance of the disease remain unknown, but polluting toxic molecules are incriminated more and more. In Africa, neurodegenerative diseases of the Parkinson's type are increasingly present and a parallel seems to exist between the increase in cases and the presence of toxic and polluting products such as metals. My Web conference will focus on this aspect, i.e. present experimental arguments which reinforce the hypothesis of the incrimination of these pollutants in the incidence of Parkinson's disease and / or Parkinsonism. Among the lines of research that we have developed in my laboratory in Rabat, Morocco, I have chosen this one knowing that many of our PhD students and IBRO Alumni are working or trying to develop scientific research on neurotoxicity in correlation with pathologies of the brain.
Logical Neural Networks
The work to be presented in this talk proposes a novel framework seamlessly providing key properties of both neural nets (learning) and symbolic logic (knowledge and reasoning). Every neuron has a meaning as a component of a formula in a weighted real-valued logic, yielding a highly interpretable disentangled representation. Inference is omnidirectional rather than focused on predefined target variables, and corresponds to logical reasoning, including classical first-order logic theorem proving as a special case. The model is end-to-end differentiable, and learning minimizes a novel loss function capturing logical contradiction, yielding resilience to inconsistent knowledge. It also enables the open-world assumption by maintaining bounds on truth values which can have probabilistic semantics, yielding resilience to incomplete knowledge.
Epigenetics and Dementia: Lessons From the 20-Year Indianapolis-Ibadan Dementia Study
Dementia is of global interest because of the rapid increase in both the number of individuals affected and the population at risk. It is essential that the risk factors be carefully delineated for the formulation of preventive strategies. Epigenetics refers to external modifications that turn genes "on" or "off”, and cross-cultural studies of migrant populations provide information on the interplay of environmental factors on genetic predisposition. The Indianapolis-Ibadan Dementia Study compared the prevalence, incidence and risk factors of dementia in African Americans and Yoruba to tease out the role of epigenetics in dementia. The presentation will provide details on biomarkers of dementia, vascular risk factors and the association with apolipoprotein E in the Yoruba. The purpose will be to inspire early career researchers on possibilities and research strategies applicable in African populations
African Neuroscience: Current Status and Prospects
Understanding the function and dysfunction of the brain remains one of the key challenges of our time. However, an overwhelming majority of brain research is carried out in the Global North, by a minority of well-funded and intimately interconnected labs. In contrast, with an estimated one neuroscientist per million people in Africa, news about neuroscience research from the Global South remains sparse. Clearly, devising new policies to boost Africa’s neuroscience landscape is imperative. However, the policy must be based on accurate data, which is largely lacking. Such data must reflect the extreme heterogeneity of research outputs across the continent’s 54 countries. We have analysed all of Africa’s Neuroscience output over the past 21 years and uniquely verified the work performed in African laboratories. Our unique dataset allows us to gain accurate and in-depth information on the current state of African Neuroscience research, and to put it into a global context. The key findings from this work and recommendations on how African research might best be supported in the future will be discussed.
The Genetics of Parkinson's Disease: Understanding the Differences Between European and African Populations
In this talk, Professor Hardy will discuss the different causes and predispositions of PD that exist in Africa, and the differences to European populations. He will go on to discuss the importance of highlighting these differences and the impact of this vital research to people living with PD in Africa, as well as their families and caregivers.
Mini-symposium on the Neuroscience of Cognitive Development
Speakers will highlight research on the developmental processes underlying cognitive control and the effects of environmental risk factors on neural pathways in human cognitive development. Gaia Scerif, from University of Oxford, will be giving a talk on Using developmental cognitive neuroscience tools to investigate mechanisms of atypical cognitive control, followed by Kirsten Donald, from University of Cape Town, who will give a talk titled Neuroimaging the very young high risk brain: lessons from a south African birth cohort.
Quantum effects in the brain - a viable assumption?
Neuroscience Investigations in the Virgin Lands of African Biodiversity
Africa is blessed with a rich diversity and abundance in rodent and avian populations. This natural endowment on the continent portends research opportunities to study unique anatomical profiles and investigate animal models that may confer better neural architecture to study neurodegenerative diseases, adult neurogenesis, stroke and stem cell therapies. To this end, African researchers are beginning to pay closer attention to some of her indigenous rodents and birds in an attempt to develop spontaneous laboratory models for homegrown neuroscience-based research. For this presentation, I will be showing studies in our lab, involving cellular neuroanatomy of two rodents, the African giant rat (AGR) and Greater cane rat (GCR), Eidolon Bats (EB) and also the Striped Owl (SO). Using histological stains (Cresyl violet and Rapid Golgi) and immunohistochemical biomarkers (GFAP, NeuN, CNPase, Iba-1, Collagen 2, Doublecortin, Ki67, Calbindin, etc), and Electron Microscopy, morphology and functional organizations of neuronal and glial populations of the AGR , GCR, EB and SO brains have been described, with our work ongoing. In addition, the developmental profiles of the prenatal GCR brains have been chronicled across its entire gestational period. Brains of embryos/foetuses were harvested for gross morphological descriptions and then processed using immunofluorescence biomarkers to determine the pattern, onset, duration and peak of neurogenesis (Pax6, Tbr1, Tbr2, NF, HuCD, MAP2) and the onset and peak of glial cell expressions and myelination in the prenatal GCR. The outcome of these research efforts has shown unique neuroanatomical expressions and networks amongst Africa’s rich biodiversity. It is hopeful that continuous effort in this regard will provide sufficient basic research data on neural developments and cellular neuroanatomy with subsequent translational consequences.
IMMUNOHISTOCHEMICAL CHARACTERIZATION OF THE RETINA–OPTIC NERVE–BRAIN VISUAL PATHWAY IN THE AFRICAN TREE SQUIRREL
FENS Forum 2026
Gene Therapy Research and the Brain: Is Africa Ethically, Legally and Socially Ready?
The influence of childhood trauma and epigenetic variation in OXTR on anxiety proneness and structural neuroimaging measures in a South African adolescent cohort
Cross-cultural cognition: Working memory in South African young adults
FENS Forum 2024
Investigating lipid droplet regulation and microglia activation as intrinsic adaptations in brains of the African naked mole rat
FENS Forum 2024
A maternal diet enriched with African walnuts confers neurodevelopmental resilience to MnCl2-induced neurotoxic cascades in rats
FENS Forum 2024
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