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  • 1
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 378, No. 6615 ( 2022-10-07)
    Abstract: 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. Expanse of SARS-CoV-2 sequencing capacity in Africa. ( A ) African countries (shaded in gray) and institutions (red circles) with on-site sequencing facilities that are capable of producing SARS-CoV-2 whole genomes locally. ( B ) The number of SARS-CoV-2 genomes produced per country and the proportion of those genomes that were produced locally, regionally within Africa, or abroad. ( C ) Decreased turnaround time of sequencing output in Africa to an almost real-time release of genomic data.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
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    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2022
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  • 2
    In: Annals of Biomedical Engineering, Springer Science and Business Media LLC, Vol. 46, No. 10 ( 2018-10), p. 1534-1547
    Type of Medium: Online Resource
    ISSN: 0090-6964 , 1573-9686
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
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  • 3
    In: The Journal of Thoracic and Cardiovascular Surgery, Elsevier BV, Vol. 153, No. 4 ( 2017-04), p. 934-943
    Type of Medium: Online Resource
    ISSN: 0022-5223
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
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  • 4
    In: Science Robotics, American Association for the Advancement of Science (AAAS), Vol. 2, No. 12 ( 2017-11-22)
    Abstract: Previous soft robotic ventricular assist devices have generally targeted biventricular heart failure and have not engaged the interventricular septum that plays a critical role in blood ejection from the ventricle. We propose implantable soft robotic devices to augment cardiac function in isolated left or right heart failure by applying rhythmic loading to either ventricle. Our devices anchor to the interventricular septum and apply forces to the free wall of the ventricle to cause approximation of the septum and free wall in systole and assist with recoil in diastole. Physiological sensing of the native hemodynamics enables organ-in-the-loop control of these robotic implants for fully autonomous augmentation of heart function. The devices are implanted on the beating heart under echocardiography guidance. We demonstrate the concept on both the right and the left ventricles through in vivo studies in a porcine model. Different heart failure models were used to demonstrate device function across a spectrum of hemodynamic conditions associated with right and left heart failure. These acute in vivo studies demonstrate recovery of blood flow and pressure from the baseline heart failure conditions. Significant reductions in diastolic ventricle pressure were also observed, demonstrating improved filling of the ventricles during diastole, which enables sustainable cardiac output.
    Type of Medium: Online Resource
    ISSN: 2470-9476
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2017
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  European Journal of Cardio-Thoracic Surgery Vol. 53, No. 5 ( 2018-05-01), p. 939-944
    In: European Journal of Cardio-Thoracic Surgery, Oxford University Press (OUP), Vol. 53, No. 5 ( 2018-05-01), p. 939-944
    Type of Medium: Online Resource
    ISSN: 1010-7940 , 1873-734X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 6
    In: European Journal of Cardio-Thoracic Surgery, Oxford University Press (OUP), Vol. 62, No. 4 ( 2022-09-02)
    Abstract: OBJECTIVES Among patients with hypoplastic left heart syndrome (HLHS), tricuspid valve regurgitation (TR) portends a poor prognosis. Our goal was to describe the outcomes of tricuspid valve reconstruction (TVR) concomitant with the Norwood operation and using two-dimensional echocardiography and evaluate the structural factors associated with successful functional correction. METHODS We performed a retrospective, single-centre study of patients with HLHS undergoing TVR at the time of the Norwood operation. Structural echocardiographic parameters were compared between patients with successful correction (≤ mild TR) and those with ≥ moderate regurgitation at discharge. Preoperative dimensions of matched HLHS controls with ≤ trivial TR were used as a reference. RESULTS Of 205 patients with HLHS undergoing the Norwood operation, 18 patients had a concomitant TVR. Ten (56%) patients had an improved TR grade postoperatively, 8 (44%) of whom had ≤ mild TR at discharge. Improvement in TR grade (P = 0.001) and having ≤ mild TR at discharge (P = 0.011) were associated with an improved reintervention and TR-free survival. Patients with successful functional correction had smaller preoperative tricuspid annulus lateral dimensions (P = 0.023), tricuspid valve area (P = 0.007) and right ventricle mid-width (P = 0.064). Preoperatively, the successful TVR cases tended to have had higher anterior leaflet excursion (80 ± 20 vs 55 ± 11, P = 0.010), and a higher proportion of anterior leaflet prolapse (63% vs 10%, P = 0.043) compared to cases where TVR was not successful. CONCLUSIONS Patients with HLHS with significant tricuspid regurgitation undergoing the stage 1 operation were more likely to have successful concomitant tricuspid valve repair if they had less tricuspid annular dilation, less-severe RV enlargement and predominantly anterior leaflet prolapse. Successful tricuspid valve repair was associated with improved mid- and long-term outcomes.
    Type of Medium: Online Resource
    ISSN: 1010-7940 , 1873-734X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 7
    In: Xenotransplantation, Wiley, Vol. 20, No. 6 ( 2013-11), p. 458-468
    Abstract: The development of genetically modified pigs, which lack the expression of alpha 1‐3 galactosyl transferase, (GalT‐ KO pigs) has facilitated the xenogeneic transplantation of porcine organs and tissues into primates by avoiding hyperacute rejection due to pre‐existing antibodies against the Gal epitope. However, antibodies against other antigens (anti‐non‐Gal antibodies), are found at varying levels in the pre‐transplant sera of most primates. We have previously found that baboons with high levels of pre‐transplant anti‐non‐Gal IgG, conditioned with a non‐myeloablative conditioning regimen, failed to engraft following pig‐to‐baboon bone marrow transplantation (Xenotransplantation, 17, 2010 and 300). Two baboons with low levels of pre‐transplant anti‐non‐Gal IgG, conditioned with the same regimen, showed porcine bone marrow progenitors at 28 days following transplantation, suggesting engraftment. These baboons also showed evidence of donor‐specific hyporesponsiveness. This observation led us to investigate the hypothesis that selecting for baboon recipients with low pre‐transplant anti‐non‐Gal IgG levels might improve engraftment levels following GalT‐ KO pig‐to‐baboon bone marrow transplantation. Methods Five baboons, with low pre‐transplant anti‐non‐Gal IgG levels, received transplantation of bone marrow cells (1–5 × 10 9 /kg of recipient weight) from GalT‐ KO pigs. They received a non‐myeloablative conditioning regimen consisting of low‐dose total body irradiation (TBI) (150 cGy), thymic irradiation (700 cGy), anti‐thymocyte globulin ( ATG ), and tacrolimus. In addition, two baboons received Rituximab and Bortezomib (Velcade) treatment as well as extra‐corporeal immunoadsorption using GalT‐ KO pig livers. Bone marrow engraftment was assessed by porcine‐specific PCR on colony forming units ( CFU ) of day 28 bone marrow aspirates. Anti‐non‐Gal antibody levels were assessed by serum binding toward GalT‐ KO PBMC using flow cytometry ( FACS ). Peripheral macro‐chimerism was measured by FACS using pig and baboon‐specific antibodies and baboon anti‐pig cellular responses were assessed by mixed lymphocyte reactions ( MLR ). Results As previously reported, two of five baboons demonstrated detectable bone marrow engraftment at 4 weeks after transplantation. Engraftment was associated with lack of an increase in anti‐non‐Gal IgG levels as well as cellular hyporesponsiveness toward pig. Three subsequent baboons with similarly low levels of pre‐existing anti‐non‐Gal IgG showed no engraftment and an increase in anti‐non‐Gal IgG antibody levels following transplantation. Peripheral macrochimerism was only seen for a few days following transplantation regardless of antibody development. Conclusions Selecting for baboon recipients with low levels of pre‐transplant anti‐non‐Gal IgG did not ensure bone marrow engraftment. Failure to engraft was associated with an increase in anti‐non‐Gal IgG levels following transplantation. These results suggest that anti‐non‐Gal‐IgG is likely involved in early bone marrow rejection and that successful strategies for combating anti‐non‐Gal IgG development may allow better engraftment. Since engraftment was only low and transient regardless of antibody development, innate immune, or species compatibility mechanisms will likely also need to be addressed to achieve long term engraftment.
    Type of Medium: Online Resource
    ISSN: 0908-665X , 1399-3089
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
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  • 8
    In: Interactive CardioVascular and Thoracic Surgery, Oxford University Press (OUP), Vol. 35, No. 5 ( 2022-10-10)
    Abstract: OBJECTIVES The goal of this study was to describe the factors affecting mid and late aortic remodelling following thoracic endovascular aortic repair with the PETTICOAT (Provisional Extension To Induce Complete Attachment) technique among patients with complicated acute or subacute type B aortic dissection. METHODS A retrospective single-centre study that evaluates clinical and morphological outcomes among 65 consecutive patients. The area and diameter of the true and false lumen, overall aortic diameter and false lumen perfusion were evaluated. RESULTS Concomitant direct visceral artery stenting was successfully conducted in 32 (49%) patients. There was one (1.5%) postoperative stroke; three (4.6%) patients developed spinal cord ischaemia; two (3%) patients suffered retrograde type A dissection; and two (3%) patients had mesenteric ischaemia, despite successful reperfusion, that required a bowel resection. Median postoperative follow-up was 63.1 (interquartile range, 32.1– 91.8) months. The probability of survival was 96.9% [95% confidence interval (CI) 88.3%–99.2%] at 30 days, 93.9% (95% CI 84.4%–97.6%) at 1 year, 78.0 (95% CI 64.2%–87.0%) at 5 years and 72.8% (95% CI at 57.9%–83.2%) at 10 years postoperatively. There was a statistically significant postoperative increase in true-lumen area, diameter and true-lumen index in all five aortic levels measured. Complete false lumen (FL) thrombosis at the coeliac trunk, renal arteries and aortic bifurcation levels was observed in 47%, 15% and 24% of patients at midterm (6–15 months) and in 29%, 21% and 29% on late (later than 21 months) computed tomography angiograms (CTA). Persistent false lumen (FL) perfusion at the coeliac level on midterm CTA was associated with a larger extent of late aortic growth (P = 0.042) and was, in the majority of cases, caused by iliac re-entries either alone (28.57) or in combination with visceral and lumbar (28.57%) or distal aortic (10.71%) re-entries. A larger abdominal aortic diameter at midterm was associated with an increased probability of distal aortic reinterventions (hazard ratio 7.26, 95% CI 2.41–21.9, P  & lt; 0.001). CONCLUSIONS Persistent FL perfusion of the distal aorta at midterm following TEVAR with the PETTICOAT technique among patients with acute and subacute type B dissection is caused mainly by iliac, visceral, lumber and distal aorta re-entries. Patients with persistent FL perfusion have an increased risk of aortic aneurysmal growth at late follow-up.
    Type of Medium: Online Resource
    ISSN: 1569-9285
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 9
    In: JACC: Cardiovascular Imaging, Elsevier BV, Vol. 13, No. 9 ( 2020-09), p. 2036-2042
    Type of Medium: Online Resource
    ISSN: 1936-878X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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  • 10
    In: JACC: Basic to Translational Science, Elsevier BV, Vol. 5, No. 3 ( 2020-03), p. 229-242
    Type of Medium: Online Resource
    ISSN: 2452-302X
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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