Implementation of and Early Outcomes From Anal Cancer Screening at a Community-Engaged Health Care Facility Providing Care to Nigerian Men Who Have Sex With Men.

PurposeAnal cancer risk is substantially higher among HIV-infected men who have sex with men (MSM) as compared with other reproductive-age adults, but screening is rare across sub-Saharan Africa. We report the use of high-resolution anoscopy (HRA) as a first-line screening tool and the resulting early outcomes among MSM in Abuja, Nigeria.MethodsFrom August 2016 to August 2017, 424 MSM enrolled in an anal cancer screening substudy of TRUST/RV368, a combined HIV prevention and treatment cohort. HRA-directed biopsies were diagnosed by histology, and ablative treatment was offered for high-grade squamous intraepithelial lesions (HSIL). HRA proficiency was assessed by evaluating the detection of squamous intraepithelial lesions (SIL) over time and the proportion biopsied. Prevalence estimates of low-grade squamous intraepithelial lesions and HSIL with 95% CIs were calculated. Multinomial logistic regression was used to identify those at the highest risk of SIL.ResultsMedian age was 25 years (interquartile range [IQR], 22-29), median time since sexual debut was 8 years (IQR, 4-12), and 59% (95% CI, 54.2% to 63.6%) were HIV infected. Rate of detection of any SIL stabilized after 200 screenings, and less than 20% had two or more biopsies. Preliminary prevalence estimates of low-grade squamous intraepithelial lesions and HSIL were 50.0% (95% CI, 44.7% to 55.3%) and 6.3% (95% CI, 4.0% to 9.3%). HIV infection, at least 8 years since anal coital debut, concurrency, and external warts were independently statistically associated with SIL.ConclusionProficiency with HRA increased with experience over time. However, HSIL detection rates were low, potentially affected by obstructed views from internal warts and low biopsy rates, highlighting the need for ongoing evaluation and mentoring to validate this finding. HRA is a feasible first-line screening tool at an MSM-friendly health care facility. Years since anal coital debut and external warts could prioritize screening

Development of MKIDs in the Optical and Near-infrared Bands for SPIAKID

SpectroPhotometric Imaging in Astronomy with Kinetic Inductance Detectors (SPIAKID) aims at designing, building, and deploying on the sky a spectrophotometric imager based on microwave kinetic inductance detectors (MKIDs) in the optical and near-infrared bands. MKIDs show a fast response and the ability to resolve photon energy compared to the conventional Charge-coupled Devices (CCDs). In this paper, we present the design and simulation of the MKID arrays for SPIAKID. The detectors consist of four arrays with each array of 20,000 lumped-element pixels, and each array will be read with 10 readout lines. %The array is designed to have resonances between 4-8GHz with a frequency spacing of 2 MHz and a coupling quality factor (Qc) of about 50000. The meander material of the resonators is trilayer TiN/Ti/TiN to have better uniformity of the critical temperature across the array. We also present the measurement result for a test array with $30\times30$ pixels which is a subset of the designed 2000-pixel array to verify the design and fabrication. The current measured best energy resolving power $R = E/\Delta E$ is 2.4 at $\lambda = 405~$nm and the current medium R is around 1.7. We have also observed the response of the TiN/Ti/TiN is much smaller than expected.Comment: 9 pages, 6 figures. Accepted by the Journal of Low Temperature Physic

Cellular senescence in progenitor cells contributes to diminished remyelination potential in progressive multiple sclerosis

Cellular senescence is a form of adaptive cellular physiology associated with aging. Cellular senescence causes a proinflammatory cellular phenotype that impairs tissue regeneration, has been linked to stress, and is implicated in several human neurodegenerative diseases. We had previously determined that neural progenitor cells (NPCs) derived from induced pluripotent stem cell (iPSC) lines from patients with primary progressive multiple sclerosis (PPMS) failed to promote oligodendrocyte progenitor cell (OPC) maturation, whereas NPCs from age-matched control cell lines did so efficiently. Herein, we report that expression of hallmarks of cellular senescence were identified in SOX2+ progenitor cells within white matter lesions of human progressive MS (PMS) autopsy brain tissues and iPS-derived NPCs from patients with PPMS. Expression of cellular senescence genes in PPMS NPCs was found to be reversible by treatment with rapamycin, which then enhanced PPMS NPC support for oligodendrocyte (OL) differentiation. A proteomic analysis of the PPMS NPC secretome identified high-mobility group box-1 (HMGB1), which was found to be a senescence-associated inhibitor of OL differentiation. Transcriptome analysis of OPCs revealed that senescent NPCs induced expression of epigenetic regulators mediated by extracellular HMGB1. Lastly, we determined that progenitor cells are a source of elevated HMGB1 in human white matter lesions. Based on these data, we conclude that cellular senescence contributes to altered progenitor cell functions in demyelinated lesions in MS. Moreover, these data implicate cellular aging and senescence as a process that contributes to remyelination failure in PMS, which may impact how this disease is modeled and inform development of future myelin regeneration strategies

Échecs thérapeutiques chez les enfants infectés par le VIH en suivi de routine dans un contexte à ressources limitées au Cameroun

Abstract Introduction: L'objectif de cette étude était de déterminer les facteurs associés aux échecs thérapeutiques chez les enfants infectés par le VIH

Cohort profile: effect of malaria in early pregnancy on fetal growth in Benin (RECIPAL preconceptional cohort).

PURPOSE: REtard de Croissance Intra-uterin et PALudisme (RECIPAL) is an original preconceptional cohort designed to assess the consequences of malaria during the first trimester of pregnancy, which is a poorly investigated period in Africa and during which malaria may be detrimental to the fetus. PARTICIPANTS: For this purpose, a total of 1214 women of reproductive age living in Sô-Ava and Akassato districts (south Benin) were followed up monthly from June 2014 to December 2016 until 411 of them became pregnant. A large range of health determinants was collected both before and during pregnancy from the first weeks of gestation to delivery. Five Doppler ultrasound scans were performed for early dating of the pregnancy and longitudinal fetal growth assessment. FINDINGS TO DATE: Pregnant women were identified at a mean of 6.9 weeks of gestation (wg). Preliminary results confirmed the high prevalence of malaria in the first trimester of pregnancy, with more than 25.4% of women presenting at least one microscopic malarial infection during this period. Most infections occurred before six wg. The prevalence of low birth weight, small birth weight for gestational age (according to INTERGROWTH-21st charts) and preterm birth was 9.3%, 18.3% and 12.6%, respectively. FUTURE PLANS: REtard de Croissance Intra-uterin et PALudisme (RECIPAL) represents at this time a unique resource that will provide information on multiple infectious (including malaria), biological, nutritional and environmental determinants in relation to health outcomes in women of reproductive age, pregnant women and their newborns. It will contribute to better define future recommendations for the prevention of malaria in early pregnancy and maternal malnutrition in Africa. It confirms that it is possible to constitute a preconceptional pregnancy cohort in Africa and provides valuable information for researchers starting cohorts in the future

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Développement de Détecteurs à Inductance Cinétique pour le Visible et l'Infrarouge Proche en Astronomie

Microwave Kinetic Inductance Detectors (MKIDs) are superconductive thin films LCresonators with high quality factors. They can simultaneously record single-photon eventsand measure their energy without any added optics. Combined with the ease ofmultiplexing thousands of pixels into a large array, MKIDs are now at the heart of currentand upcoming ground-based astronomy applications. Among them is theSpectroPhotometric Imaging for Astronomy with Kinetic Inductance Detectors (SPIAKID)project at Paris Observatory. We are using MKID technology to build a 20,000 pixelsspectrophotometer that will be deployed in 2024 on the 3.58m New TechnologyTelescope (NTT) in Chile. SPIAKID aims to study the population and metallicity of stars inUltra Faint Dwarf (UFD) galaxies in the Local group to have a better understanding ofgalaxy formation and evolution. We will present an original design intended to improvethe optical coupling between incident photons and the absorber part of the detector aswell as an anomalous response from our superconductor that could offer a new mean ofdetectionLes détecteurs à inductance cinétique (MKIDs) sont des résonateurs LC à haut facteurde qualité faits à partir de couches minces supraconductrices. Ils peuvent simultanémentdéterminer le temps d'arrivée de chaque photon en mesurant leur énergie sans optiquesupplémentaire. Grâce au pouvoir de multiplexage des MKIDs qui permet de facilementréaliser des matrices de plusieurs kilopixels, cette technologie est au centre de l'attentionpour les nouvelles applications en astronomie. Parmi eux se trouve l'instrumentSpectroPhotometric Imaging for Astronomy with Kinetic Inductance Detectors (SPIAKID),projet du GEPI à l'Observatoire de Paris. Nous utilisons la technologie MKID pourconstruire un spectrophotomètre composé de 20 000 pixels qui sera déployé sur le NewTechnology Telescope (NTT) de 3.6m au Chili à l'horizon 2025. SPIAKID s'intéressera àla population stellaire des galaxies naines ultra faibles du Groupe Local pour mieuxcomprendre la formation des galaxies ainsi que la matière noire. Nous présenterons dansce travail de thèse un design novateur pour améliorer le couplage optique entre lesphotons incidents et la partie sensible du détecteur ainsi qu'une réponse anormale denotre supraconducteur qui pourrait faire l'objet d'un nouveau moyen de détection

Development of Microwave KineticInductance Detectors for Visible andNear-IR Astronomy Applications

Les détecteurs à inductance cinétique (MKIDs) sont des résonateurs LC à haut facteur de qualité faits à partir de couches minces supraconductrices. Ils peuvent simultanément déterminer le temps d'arrivée de chaque photon en mesurant leur énergie sans optique supplémentaire. Grâce au pouvoir de multiplexage des MKIDs qui permet de facilement réaliser des matrices de plusieurs kilopixels, cette technologie est au centre de l'attention pour les nouvelles applications en astronomie. Parmi eux se trouve l'instrument SpectroPhotometric Imaging for Astronomy with Kinetic InductanceDetectors (SPIAKID), projet du GEPI à l'Observatoire de Paris. Nous utilisons la technologie MKID pour construire un spectrophotomètre composé de 20 000 pixels qui sera déployé sur le New Technology Telescope (NTT) de 3.6m au Chili à l'horizon 2025. SPIAKID s'intéressera à la population stellaire des galaxies naines ultra faibles du Groupe Local pour mieux comprendre la formation des galaxies ainsi que la matière noire. Nous présenterons dans ce travail de thèse un design novateur pour améliorer le couplage optique entre les photons incidents et la partie sensible du détecteur.Microwave Kinetic Inductance Detectors (MKIDs) are superconductive thin films LCresonators with high quality factors. They can simultaneously record single-photon events and measure their energy without any added optics. Combined with the ease of multiplexing thousands of pixels into a large array, MKIDs are now at the heart of current and upcoming ground-based astronomy applications .Among them is the SpectroPhotometric Imaging for Astronomy with Kinetic InductanceDetectors (SPIAKID) project at Paris Observatory. We are using MKID technologyto build a 20,000 pixels spectrophotometer that will be deployed in 2025 on the 3.6m New Technology Telescope (NTT) in Chile. SPIAKID aims to study the population andmetallicity of stars in Ultra Faint Dwarf (UFD) galaxies in the Local group to have abetter understanding of galaxy formation and evolution. We will present an original design intended to improve the optical coupling between incident photons and the absorber part of the detector