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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: Diabetes, American Diabetes Association, Vol. 72, No. 8 ( 2023-08-01), p. 1161-1172
    Abstract: Genome-wide significant loci for metformin response in type 2 diabetes reported elsewhere have not been replicated in the Diabetes Prevention Program (DPP). To assess pharmacogenetic interactions in prediabetes, we conducted a genome-wide association study (GWAS) in the DPP. Cox proportional hazards models tested associations with diabetes incidence in the metformin (MET; n = 876) and placebo (PBO; n = 887) arms. Multiple linear regression assessed association with 1-year change in metformin-related quantitative traits, adjusted for baseline trait, age, sex, and 10 ancestry principal components. We tested for gene-by-treatment interaction. No significant associations emerged for diabetes incidence. We identified four genome-wide significant variants after correcting for correlated traits (P & lt; 9 × 10−9). In the MET arm, rs144322333 near ENOSF1 (minor allele frequency [MAF]AFR = 0.07; MAFEUR = 0.002) was associated with an increase in percentage of glycated hemoglobin (per minor allele, β = 0.39 [95% CI 0.28, 0.50] ; P = 2.8 × 10−12). rs145591055 near OMSR (MAF = 0.10 in American Indians) was associated with weight loss (kilograms) (per G allele, β = −7.55 [95% CI −9.88, −5.22]; P = 3.2 × 10−10) in the MET arm. Neither variant was significant in PBO; gene-by-treatment interaction was significant for both variants [P(G×T) & lt; 1.0 × 10−4]. Replication in individuals with diabetes did not yield significant findings. A GWAS for metformin response in prediabetes revealed novel ethnic-specific associations that require further investigation but may have implications for tailored therapy.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2023
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  • 3
    In: Diabetes Care, American Diabetes Association, Vol. 45, No. 7 ( 2022-07-07), p. 1640-1646
    Abstract: To determine whether interventions that slow or prevent the development of type 2 diabetes in those at risk reduce the subsequent prevalence of diabetic retinopathy. RESEARCH DESIGN AND METHODS The Diabetes Prevention Program (DPP) randomized subjects at risk for developing type 2 diabetes because of overweight/obesity and dysglycemia to metformin (MET), intensive lifestyle intervention (ILS), or placebo (PLB) to assess the prevention of diabetes. During the DPP and DPP Outcome Study (DPPOS), we performed fundus photography over time on study participants, regardless of their diabetes status. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study grading system, with diabetic retinopathy defined as typical lesions of diabetic retinopathy (microaneurysms, exudates, or hemorrhage, or worse) in either eye. RESULTS Despite reduced progression to diabetes in the ILS and MET groups compared with PLB, there was no difference in the prevalence of diabetic retinopathy between treatment groups after 1, 5, 11, or 16 years of follow-up. No treatment group differences in retinopathy were found within prespecified subgroups (baseline age, sex, race/ethnicity, baseline BMI). In addition, there was no difference in the prevalence of diabetic retinopathy between those exposed to metformin and those not exposed to metformin, regardless of treatment group assignment. CONCLUSIONS Interventions that delay or prevent the onset of type 2 diabetes in overweight/obese subjects with dysglycemia who are at risk for diabetes do not reduce the development of diabetic retinopathy for up to 20 years.
    Type of Medium: Online Resource
    ISSN: 0149-5992
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
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  • 4
    In: Diabetes Care, American Diabetes Association, Vol. 42, No. 9 ( 2019-09-01), p. 1809-1815
    Abstract: Regression from prediabetes to normal glucose regulation (NGR) was associated with reduced incidence of diabetes by 56% over 10 years in participants in the Diabetes Prevention Program Outcomes Study (DPPOS). In an observational analysis, we examined whether regression to NGR also reduced risk for microvascular disease (MVD). RESEARCH DESIGN AND METHODS Generalized estimating equations were used to examine the prevalence of aggregate MVD at DPPOS year 11 in people who regressed to NGR at least once (vs. never) during the Diabetes Prevention Program (DPP). Logistic regression assessed the relationship of NGR with retinopathy, nephropathy, and neuropathy, individually. Generalized additive models fit smoothing splines to describe the relationship between average A1C during follow-up and MVD (and its subtypes) at the end of follow-up. RESULTS Regression to NGR was associated with lower prevalence of aggregate MVD in models adjusted for age, sex, race/ethnicity, baseline A1C, and treatment arm (odds ratio [OR] 0.78, 95% CI 0.65–0.78, P = 0.011). However, this association was lost in models that included average A1C during follow-up (OR 0.95, 95% CI 0.78–1.16, P = 0.63) or diabetes status at the end of follow-up (OR 0.92, 95% CI 0.75–1.12, P = 0.40). Similar results were observed in examination of the association between regression to NGR and prevalence of nephropathy and retinopathy, individually. Risk for aggregate MVD, nephropathy, and retinopathy increased across the A1C range. CONCLUSIONS Regression to NGR is associated with a lower prevalence of aggregate MVD, nephropathy, and retinopathy, primarily due to lower glycemic exposure over time. Differential risk for the MVD subtypes begins in the prediabetes A1C range.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2019
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  • 5
    In: South African Journal of Science, Academy of Science of South Africa, Vol. 112, No. 9/10 ( 2016-09-28), p. 4-
    Type of Medium: Online Resource
    ISSN: 1996-7489
    Language: Unknown
    Publisher: Academy of Science of South Africa
    Publication Date: 2016
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  • 6
    Online Resource
    Online Resource
    Frontiers Media SA ; 2019
    In:  Frontiers in Marine Science Vol. 6 ( 2019-11-19)
    In: Frontiers in Marine Science, Frontiers Media SA, Vol. 6 ( 2019-11-19)
    Type of Medium: Online Resource
    ISSN: 2296-7745
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2019
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  • 7
    In: Diabetologia, Springer Science and Business Media LLC, Vol. 66, No. 7 ( 2023-07), p. 1260-1272
    Type of Medium: Online Resource
    ISSN: 0012-186X , 1432-0428
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
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  • 8
    In: Fisheries Oceanography, Wiley, Vol. 29, No. 2 ( 2020-03), p. 137-151
    Abstract: This study applied a previously used Lagrangian individual‐based model (IBM) for sardine in the Southern Benguela to an improved and more robust hydrodynamic model to investigate whether a more representative spatial coverage, greater horizontal and vertical resolution, more realistic winds and improved representation of mesoscale features such as eddies and filaments would give different results for transport and retention of early life stages. Despite major differences between the old and new hydrodynamic models, overall the IBM results were quite similar to the previous southern Benguela sardine IBM study. This surprising result indicates that it is the macroscale circulation features resolved by the two hydrodynamic models that are controlling transport and retention of sardine early life stages. The contribution of transient mesoscale features such as eddies and filaments appears to be less important when transport patterns are averaged over the 21‐year‐long experiment. Another aim of this study was to better estimate the contribution of south coast spawning to west coast sardine recruitment. This was possible because of an eastward extension of the geographical domain of the new hydrodynamic model which provided a more realistic representation of the south coast spawning ground. Three main spawning and nursery area systems, similar to those identified in the previous sardine IBM, were identified: west coast and west coast (WC‐WC), south coast and west coast (SC‐WC), and south coast and south coast (SC‐SC). Spawning area proved to be an important determinant of modelled retention and transport success, with spawning depth also playing an important role on the west coast. The main difference observed from the previous study was an increase in the average percentage of particles released on the south coast and transported to the west coast (P 0 , 17.4%). This indicates more connectivity between the southern and western sardine stocks than previously thought and is therefore important for fishery management. Standardized anomalies from the modelled retention/transport were compared with recruitment estimates from stock assessment models but there was no correlation between the two sets of anomalies. However, a significant correlation was observed between the modelled retention/transport anomalies for the west coast and total cumulative upwelling anomalies for the Southern Benguela ( r  = −0.67, p   〈  .001).
    Type of Medium: Online Resource
    ISSN: 1054-6006 , 1365-2419
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2020
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  • 9
    Online Resource
    Online Resource
    American Geophysical Union (AGU) ; 2018
    In:  Eos Vol. 99 ( 2018-06-12)
    In: Eos, American Geophysical Union (AGU), Vol. 99 ( 2018-06-12)
    Abstract: Off the east coast of South Africa, robotic ocean gliders deployed in the Agulhas Current capture new data that help us better understand how energy dissipates in the ocean.
    Type of Medium: Online Resource
    ISSN: 2324-9250
    Language: Unknown
    Publisher: American Geophysical Union (AGU)
    Publication Date: 2018
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  • 10
    In: JAMA Ophthalmology, American Medical Association (AMA), Vol. 141, No. 2 ( 2023-02-01), p. 140-
    Abstract: Age-related macular degeneration (AMD) is a leading cause of blindness with no treatment available for early stages. Retrospective studies have shown an association between metformin and reduced risk of AMD. Objective To investigate the association between metformin use and age-related macular degeneration (AMD). Design, Setting, and Participants The Diabetes Prevention Program Outcomes Study is a cross-sectional follow-up phase of a large multicenter randomized clinical trial, Diabetes Prevention Program (1996-2001), to investigate the association of treatment with metformin or an intensive lifestyle modification vs placebo with preventing the onset of type 2 diabetes in a population at high risk for developing diabetes. Participants with retinal imaging at a follow-up visit 16 years posttrial (2017-2019) were included. Analysis took place between October 2019 and May 2022. Interventions Participants were randomly distributed between 3 interventional arms: lifestyle, metformin, and placebo. Main Outcomes and Measures Prevalence of AMD in the treatment arms. Results Of 1592 participants, 514 (32.3%) were in the lifestyle arm, 549 (34.5%) were in the metformin arm, and 529 (33.2%) were in the placebo arm. All 3 arms were balanced for baseline characteristics including age (mean [SD] age at randomization, 49 [9] years), sex (1128 [71%] male), race and ethnicity (784 [49%] White), smoking habits, body mass index, and education level. AMD was identified in 479 participants (30.1%); 229 (14.4%) had early AMD, 218 (13.7%) had intermediate AMD, and 32 (2.0%) had advanced AMD. There was no significant difference in the presence of AMD between the 3 groups: 152 (29.6%) in the lifestyle arm, 165 (30.2%) in the metformin arm, and 162 (30.7%) in the placebo arm. There was also no difference in the distribution of early, intermediate, and advanced AMD between the intervention groups. Mean duration of metformin use was similar for those with and without AMD (mean [SD], 8.0 [9.3] vs 8.5 [9.3] years; P  = .69). In the multivariate models, history of smoking was associated with increased risks of AMD (odds ratio, 1.30; 95% CI, 1.05-1.61; P  = .02). Conclusions and Relevance These data suggest neither metformin nor lifestyle changes initiated for diabetes prevention were associated with the risk of any AMD, with similar results for AMD severity. Duration of metformin use was also not associated with AMD. This analysis does not address the association of metformin with incidence or progression of AMD.
    Type of Medium: Online Resource
    ISSN: 2168-6165
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2023
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