Browsing by Author "Liu, Y."
Now showing 1 - 9 of 9
Results Per Page
Sort Options
Item Assessing the impacts of COVID-19 vaccination programme’s timing and speed on health benefts, cost-efectiveness, and relative afordability in 27 African countries(BMC Medicine, 2023) Liu, Y.; Procter, S.R.; Nonvignon, J.; et al.Background The COVID-19 vaccine supply shortage in 2021 constrained roll-out efforts in Africa while populations experienced waves of epidemics. As supply improves, a key question is whether vaccination remains an impactful and cost-effective strategy given changes in the timing of implementation. Methods We assessed the impact of vaccination programme timing using an epidemiological and economic model. We fitted an age-specific dynamic transmission model to reported COVID-19 deaths in 27 African countries to approximate existing immunity resulting from infection before substantial vaccine roll-out. We then projected health outcomes (from symptomatic cases to overall disability-adjusted life years (DALYs) averted) for different programme start dates (01 January to 01 December 2021, n=12) and roll-out rates (slow, medium, fast; 275, 826, and 2066 doses/ million population-day, respectively) for viral vector and mRNA vaccines by the end of 2022. Roll-out rates used were derived from observed uptake trajectories in this region. Vaccination programmes were assumed to priorities those above 60 years before other adults. We collected data on vaccine delivery costs, calculated incremental cost-efectiveness ratios (ICERs) compared to no vaccine use, and compared these ICERs to GDP per capita. We additionally calculated a relative affordability measure of vaccination programmes to assess potential nonmarginal budget impacts. Results Vaccination programmes with early start dates yielded the most health benefits and lowest ICERs compared to those with late starts. While producing the most health benefits, fast vaccine roll-out did not always result in the lowest ICERs. The highest marginal effectiveness within vaccination programmes was found among older adults. High country income groups, high proportions of populations over 60 years or non-susceptible at the start of vaccination programmes are associated with low ICERs relative to GDP per capita. Most vaccination programmes with small ICERs relative to GDP per capita were also relatively affordable.Conclusion Although ICERs increased significantly as vaccination programmes were delayed, programmes starting late in 2021 may still generate low ICERs and manageable affordability measures. Looking forward, lower vaccine purchasing costs and vaccines with improved efficacies can help increase the economic value of COVID-19 vaccination programmes.Item Enzymatic Reconstitution and Biosynthetic Investigation of the Bacterial Carbazole Neocarazostatin A(The Journal of Organic Chemistry, 2019-11-15) Kyeremeh, K.; Liu, Y.; Su, L.; Fang, Q.; Tabudravu, J.; Yang, X.; Rickaby, K.; Trembleau, L.; Deng, Z.; Deng, H.; Yu, Y.Tricyclic carbazole is an important scaffold in many naturally occurring metabolites, as well as valuable building blocks. Here we report the reconstitution of the ring A formation of the bacterial neocarazostatin A carbazole metabolite. We provide evidence of the involvement of two unusual aromatic polyketide proteins. This finding suggests how new enzymatic activities can be recruited to specific pathways to expand biosynthetic capacities. Finally, we leveraged our bioinformatics survey to identify the untapped capacity of carbazole biosynthesisItem Eudesmane-Type Sesquiterpenes from Curcuma phaeocaulis and Their Inhibitory Activities on Nitric Oxide Production in RAW 264.7 Cells(European Journal of Organic Chemistry, 2014-09) Liu, Y.; Ma, J.; Wang, Y.; Donkor, P.O.; Li, Q.; Gao, S.; Hou, Y.; Xu, Y.; Cui, J.; Ding, L.; Zhao, F.; Kang, N.; Chen, L.; Qiu, F.Eight eudesmane-type sesquiterpenes - phaeusmanes A-H (1-8) - isolated for the first time in this work, and four others (9-12) isolated for the first time from plants in this work, together with fourteen known eudesmane derivatives, were isolated from the rhizomes of Curcuma phaeocaulis. Their structures were elucidated by 1D and 2D NMR and CD spectroscopy and HRMS. Compound 8 is the first example of a nitrogen-containing eudesmane-type sesquiterpene isolated from the genus Curcuma. Furthermore, inhibitory effects of the isolated compounds on NO production in lipopolysaccharide-activated macrophages were evaluated. Compounds 1, 6, 10, 19, 22, and 24 showed strong inhibitory activities on NO production with IC50 values of 3.2, 4.8, 1.2, 0.8, 3.8, and 0.8 μM, respectively. Preliminary structure-activity relationships for these compounds are proposed. A possible biogenetic pathway for nitrogen-containing eudesmane-type sesquiterpene 8 is postulated. Eight new sesquiterpenes (phaeusmanes A-H), together with eighteen known analogues, were isolated from the rhizomes of Curcuma phaeocaulis. Their complete structures were elucidated by NMR, MS, and CD spectroscopy. The NO inhibitory effects of the isolates are presented. A possible biogenetic pathway for N-containing eudesmane-type sesquiterpene 8 is postulated. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Item GALC deletions increase the risk of primary Open-Angle Glaucoma: The role of mendelian variants in complex disease(Public Library of Science, 2013) Liu, Y.; Gibson, J.; Wheeler, J.; Kwee, L.C.; Santiago-Turla, C.M.; Akafo, S.K.; Lichter, P.R.; Gaasterland, D.E.; Moroi, S.E.; Challa, P.; Herndon, L.W.; Girkin, C.A.; Budenz, D.L.; Richards, J.E.; Allingham, R.R.; Hauser, M.A.DNA copy number variants (CNVs) have been reported in many human diseases including autism and schizophrenia. Primary Open Angle Glaucoma (POAG) is a complex adult-onset disorder characterized by progressive optic neuropathy and vision loss. Previous studies have identified rare CNVs in POAG; however, their low frequencies prevented formal association testing. We present here the association between POAG risk and a heterozygous deletion in the galactosylceramidase gene (GALC). This CNV was initially identified in a dataset containing 71 Caucasian POAG cases and 478 ethnically matched controls obtained from dbGAP (study accession phs000126.v1.p1.) (p = 0.017, fisher's exact test). It was validated with array comparative genomic hybridization (arrayCGH) and realtime PCR, and replicated in an independent POAG dataset containing 959 cases and 1852 controls (p = 0.021, OR (odds ratio) = 3.5, 95% CI -1.1-12.0). Evidence for association was strengthened when the discovery and replication datasets were combined (p = 0.002; OR = 5.0, 95% CI 1.6-16.4). Several deletions with different endpoints were identified by array CGH of POAG patients. Homozygous deletions that eliminate GALC enzymatic activity cause Krabbe disease, a recessive Mendelian disorder of childhood displaying bilateral optic neuropathy and vision loss. Our findings suggest that heterozygous deletions that reduce GALC activity are a novel mechanism increasing risk of POAG. This is the first report of a statistically-significant association of a CNV with POAG risk, contributing to a growing body of evidence that CNVs play an important role in complex, inherited disorders. Our findings suggest an attractive biomarker and potential therapeutic target for patients with this form of POAG.Item Genome-Wide linkage scan for primary open angle glaucoma: Influences of ancestry and age at diagnosis(Public Library of Science, 2013) Crooks, K.R.; Allingham, R.R.; Qin, X.; Liu, Y.; Gibson, J.R.; Santiago-Turla, C.; Larocque-Abramson, K.R.; Del Bono, E.; Challa, P.; Herndon, L.W.; Akafo, S.; Wiggs, J.L.; Schmidt, S.; Hauser, M.A.Primary open-angle glaucoma (POAG) is the most common form of glaucoma and one of the leading causes of vision loss worldwide. The genetic etiology of POAG is complex and poorly understood. The purpose of this work is to identify genomic regions of interest linked to POAG. This study is the largest genetic linkage study of POAG performed to date: genomic DNA samples from 786 subjects (538 Caucasian ancestry, 248 African ancestry) were genotyped using either the Illumina GoldenGate Linkage 4 Panel or the Illumina Infinium Human Linkage-12 Panel. A total of 5233 SNPs was analyzed in 134 multiplex POAG families (89 Caucasian ancestry, 45 African ancestry). Parametric and non-parametric linkage analyses were performed on the overall dataset and within race-specific datasets (Caucasian ancestry and African ancestry). Ordered subset analysis was used to stratify the data on the basis of age of glaucoma diagnosis. Novel linkage regions were identified on chromosomes 1 and 20, and two previously described loci-GLC1D on chromosome 8 and GLC1I on chromosome 15-were replicated. These data will prove valuable in the context of interpreting results from genome-wide association studies for POAG.Item Investigation of known genetic risk factors for primary open angle glaucoma in two populations of African ancestry(Investigative Ophthalmology and Visual Science, 2013-08) Liu, Y.; Hauser, M.A.; Akafo, S.K.; Qin, X.; Miura, S.; Gibson, J.R.; Wheeler, J.; Gaasterland, D.E.; Challa, P.; Herndon, L.W.; Ritch, R.; Moroi, S.E.; Pasquale, L.R.; Girkin, C.A.; Budenz, D.L.; Wiggs, J.L.; Richards, J.E.; Ashley-Koch, A.E.; Allingham, R.R.Purpose. Multiple genes have been associated with primary open angle glaucoma (POAG) in Caucasian populations. We now examine the association of these loci in populations of African ancestry, populations at particularly high risk for POAG. Methods. We genotyped DNA samples from two populations: African American (1150 cases and 999 controls) and those from Ghana, West Africa (483 cases and 593 controls). Our analysis included 57 single nucleotide polymorphisms (SNPs) in five loci previously associated with POAG at the genome-wide level, including CDKN2B-AS1, TMCO1, CAV1/CAV2, chromosome 8q22 intergenic region, and SIX1/SIX6. We evaluated association in the full datasets, as well as subgroups with normal pressure glaucoma (NPG, maximum IOP ≤21 mm Hg) and high pressure glaucoma (HPG, IOP >21 mm Hg). Results. In African Americans, we identified an association of rs10120688 in the CDNK2B-AS1 region with POAG (P = 0.0020). Several other SNPs were nominally associated, but did not survive correction for multiple testing. In the subgroup analyses, significant associations were identified for rs10965245 (P = 0.0005) in the CDKN2B-AS1 region with HPG and rs11849906 in the SIX1/SIX6 region with NPG (P = 0.006). No significant association was identified with any loci in the Ghanaian samples. Conclusions. POAG genetic susceptibility alleles associated in Caucasians appear to play a greatly reduced role in populations of African ancestry. Thus, the major genetic components of POAG of African origin remain to be identified. This finding underscores the critical need to pursue large-scale genome-wide association studies in this understudied, yet disproportionately affected population. © 2013 The Association for Research in Vision and Ophthalmology, Inc.Item Magma source and tectonics of the Xiangshanzhong mafic-ultramafic intrusion in the Central Asian Orogenic Belt, NW China, traced from geochemical and isotopic signatures(Lithos, 2013-06) Tang, D.; Qin, K.; Su, B.; Sakyi, P.A.; Liu, Y.; Mao, Q.; Santosh, M.; Ma, Y.Several sulfide ore-bearing mafic-ultramafic intrusions occur along the southern margin of the Late Paleozoic Central Asian Orogenic Belt (CAOB) in north Xinjiang, NW China. Their origin, magma evolution and relationship with the Permian basalts in the region remain equivocal. In this study, we investigate the Xiangshanzhong mafic-ultramafic intrusion in eastern Tianshan, dominantly composed of diorite, hornblende gabbro, gabbro, hornblende pyroxenite, olivine websterite and lherzolite. We report the occurrence of olivine clinopyroxenite in the intrusive complex with visible pyroxene cumulate structure, high Mg, low Cr, Na, and Ti contents, and characterized by distinctively low trace element contents. Our data suggest that the clinopyroxene in the olivine clinopyroxenite probably crystallized from an earlier batch of magma. The rare earth element (REE) patterns and εNd values of the Xiangshanzhong mafic-ultramafic units suggest that these rocks represent cumulates of basaltic composition that were likely co-genetic and derived from the same magmatic source. The presence of phlogopite and amphibole, occurrence of Zr, Hf, Nb, and Ta negative anomalies, the trace element abundances of the parental magma, and the Nd isotopes (+5.9-+8.3) of whole-rocks suggest that the source of the Xiangshanzhong complexes may be a depleted mantle metasomatized by subducted slab-derived fluid or melt. Furthermore, the (87Sr/86Sr)i ratios, εNd(t) values and trace element geochemistry of whole-rock and clinopyroxene grains are consistent with those of the Permian Tuha basin basalts. The Xiangshanzhong intrusion has characteristics of both plume and subduction-related origin and we therefore speculate that the partial melting of subduction-related depleted mantle triggered by Permian plume activity during the post-collision extension regime generated the parental magmas of the Xiangshanzhong intrusion. © 2013 Elsevier B.V.Item Mitochondrial genetic background in Ghanaian patients with primary open-angle glaucoma.(Molecular Vision, 2012) Abu-Amero, K.K.; Hauser, M.A.; Mohamed, G.; Liu, Y.; Gibson, J.; Gonzalez, A.M.; Akafo, S.; Allingham, R.R.PURPOSE: Prevalence rates for primary open-angle glaucoma (POAG) are significantly higher in Africans than in European or Asians. It has been reported recently that mitochondrial DNA (mtDNA) lineages of African origin, excluding L2, conferred susceptibility to POAG in Saudi Arabia. This prompted us to test the role of mtDNA haplogroups in the incidence of POAG in the Ghanaian population who has a high frequency of L2 lineages. METHODS: DNA was extracted from two independent cohorts of clinically diagnosed POAG patients (n=373) and healthy controls (n=451). All patients and controls were from Accra and Tema (the southern region of Ghana). The hypervariable region-I (HVS-I) and coding regions comprising mtDNA haplogroup diagnostic polymorphisms were polymerase chain reaction (PCR) amplified and sequenced in all patients and controls and the haplotypes obtained were assorted into haplogroups and their frequencies compared between cohorts. RESULTS: No statistically significant differences were found in mtDNA haplogroup frequencies between POAG patients and matched controls in this cohort for the various mtDNA haplogroups tested. CONCLUSIONS: In this Ghanaian cohort, mtDNA haplogroups do not seem to confer susceptibility to POAG.Item Optineurin coding variants in Ghanaian patients with primary open-angle glaucoma(Molecular Vision, 2008) Liu, Y.; Akafo, S.; Allingham, R.R.Purpose Coding variants in the optineurin gene (OPTN, GLC1E) have been reported to play a role in primary open-angle glaucoma (POAG) in various populations. This study investigated the role of OPTN sequence variants in patients with POAG in Ghana (West Africa). Methods This is a case-control study of unrelated Ghanaian POAG cases and non-glaucomatous controls. Ascertainment criteria for POAG included the presence of glaucomatous optic nerve neuropathy, associated visual field loss, and elevated intraocular pressure (IOP) in both eyes, all in the absence of secondary causes of glaucoma. Controls had normal optic nerves, visual fields, and IOP. All the coding exons of OPTN were polymerase chain reaction (PCR) amplified and sequenced in all 140 cases and 130 controls using an ABI 3730 DNA analyzer. Results All the coding exons of OPTN were sequenced in 140 POAG patients and 130 controls. Several coding variants were identified including M98K, A134A, V147L, P292P, A301G, S321S, and E322K. Three coding variants (V147L, P292P, and A301G) have not been reported previously. There were no significant differences on the frequencies of all the identified variants between POAG cases and controls in this population.