Digital development has become a firm pillar in the national development strategies of many countries in the Global South. Although the geopolitical competition over ICTs leveraged their diplomatic ...and economic relevance in the international sphere, developing countries remain in a subordinate position in global power relations. However, while they could collectively improve their standing by uniting behind an integrated digital market, national governments in the East African Community are reluctant to implement a single digital market, leading us to inquire: What constrains digital market integration in East Africa? This article compares Rwanda and Tanzania, two relatively digitally mature but less developed countries in Sub-Saharan Africa, whereas one is a small landlocked country and the other a larger emerging economy. Following the classification of Hout and Salih, material, ideational, political, and external aspects affect a nation’s enthusiasm for regional initiatives. By examining factors related to domestic politics and political economy, this article finds that material and political factors encourage digital regionalism in Rwanda but discourage it in Tanzania; ideational factors contribute to national rather than regional unity in both countries. Yet, external factors linked to EU foreign policy and developmental cooperation seem to lead current regional projects. Therefore, this article concludes that drivers of African regionalism may turn into barriers depending on the domestic political and economic circumstances while digital market integration is currently driven by foreign players. More generally, the study contributes to the debate on African agency in ICT for development and developing countries’ capacity to overcome traditional dependency structures.
Neosartorya fumigata (Aspergillus fumigatus) is the most common cause of invasive aspergillosis, a frequently fatal lung disease primarily affecting immunocompromised individuals. This opportunistic ...fungal pathogen produces several classes of specialised metabolites including products of a branch of the ergot alkaloid pathway called fumigaclavines. The biosynthesis of the N. fumigata ergot alkaloids and their relation to those produced by alternate pathway branches in fungi from the plant-inhabiting Clavicipitaceae have been well-characterised, but the potential role of these alkaloids in animal pathogenesis has not been studied extensively. We investigated the contribution of ergot alkaloids to virulence of N. fumigata by measuring mortality in the model insect Galleria mellonella. Larvae were injected with conidia (asexual spores) of two different wild-type strains of N. fumigata and three different ergot alkaloid mutants derived by previous gene knockouts and differing in ergot alkaloid profiles. Elimination of all ergot alkaloids significantly reduced virulence of N. fumigata in G. mellonella (P < 0.0001). Mutants accumulating intermediates but not the pathway end product fumigaclavine C also were less virulent than the wild type (P < 0.0003). The data indicate that ergot alkaloids contribute to virulence of N. fumigata in this insect model and that fumigaclavine C is important for full virulence.
Accurate estimation of refractive error and ocular alignment is critical for identifying amblyopia risk factors. The 2WIN photoscreener (Adaptica) uses a novel infrared-transmitting occluder wand to ...quickly estimate intermittent deviations.
Reliability analysis.
2WIN refraction was compared to dry and cycloplegic retinoscopy and Retinomax. 2WIN “CR” function with wand was compared to cover test.
371 patients aged 6 months to 63 years (median age 6 years) had refraction, and 2WIN yielded high degrees of correlation (Pearson product-moment) on linear regression for spherical equivalent (0.73-0.79), cylinder power (0.78-0.79), J0 vector (0.79-0.83), and J45 vector (0.64-0.67). Similar proportions of 2WIN and Retinomax were within target refraction values for spherical equivalent (70% 216/310 vs 69% 212/310), cylinder power (94% 154/165 vs 90% 148/165), and cylinder axis (69% 113/165 vs 71% 118/165). 2WIN CR higher than 10 prism diopters (PD) correlated with cover test for constant and intermittent deviations (Pearson correlation 0.64-0.71). 2WIN + CR screened for 2003 American Association for Pediatric Ophthalmology and Strabismus amblyopia risk factors with 68% (965/96) sensitivity and 84% (70/83) specificity in preschool children with 53% (96/180) prescreening probability and 31% (55/177) developmental delays.
The 2WIN correlated well with examination and Retinomax. The CR function reliably estimated constant and intermittent strabismus higher than 10 PD.
•2WIN is the third commercially available infrared, multiaxial photoscreener.•2WIN developed in infrared-transmitting occluder to measure strabismus.•Compared to industry-standard Retinomax, 2WIN accurately estimated refraction.•The CR wand reliably measured strabismus greater than 10 prism diopters.•2WIN was valid at detecting amblyopia risk factors, refractive error, and strabismus.
Ergot alkaloids are specialized fungal metabolites that are important as the bases of several pharmaceuticals. Many ergot alkaloids are derivatives of lysergic acid (LA) and have vasoconstrictive ...activity, whereas several dihydrolysergic acid (DHLA) derivatives are vasorelaxant. The pathway to LA is established, with the P450 monooxygenase CloA playing a key role in oxidizing its substrate agroclavine to LA. We analyzed the activities of products of
alleles from different fungi relative to DHLA biosynthesis by expressing them in a mutant of the fungus
that accumulates festuclavine, the precursor to DHLA. Transformants expressing CloA from
×
, which oxidizes agroclavine to LA, failed to oxidize festuclavine to DHLA. In substrate feeding experiments, these same transformants oxidized exogenously supplied agroclavine to LA, indicating that a functional CloA was produced. A genomic clone of
from
, a sorghum ergot fungus that produces a DHLA derivative, was cloned and expressed in the festuclavine-accumulating mutant of
, but several introns in this genomic clone were not processed properly. Expression of a synthetic intron-free version of
resulted in the accumulation of DHLA as assessed by fluorescence high-pressure liquid chromatography (HPLC) and liquid chromatography-mass spectrometry (LC-MS). In substrate feeding experiments, the
CloA also accepted agroclavine as the substrate, oxidizing it to LA. The data indicate that a specialized allele of
is required for DHLA biosynthesis and that the pharmaceutically important compound DHLA can be produced in engineered
Ergot alkaloids are fungal metabolites that have impacted humankind historically as poisons and more recently as pharmaceuticals used to treat dementia, migraines, and other disorders. Much is known about the biosynthesis of ergot alkaloids that are derived from lysergic acid (LA), but important questions remain about a parallel pathway to ergot alkaloids derived from dihydrolysergic acid (DHLA). DHLA-derived alkaloids have minor structural differences compared to LA-derived alkaloids but can have very different activities. To understand how DHLA is made, we analyzed activities of a key enzyme in the DHLA pathway and found that it differed from its counterpart in the LA pathway. Our data indicate a critical difference between the two pathways and provide a strategy for producing DHLA by modifying a model fungus. The ability to produce DHLA in a model fungus may facilitate synthesis of DHLA-derived pharmaceuticals.
We examined the infrastructure for US public sexually transmitted disease (STD) clinical services.
In 2013 to 2014, we surveyed 331 of 1225 local health departments (LHDs) who either reported ...providing STD testing/treatment in the 2010 National Profile of Local Health Departments survey or were the 50 local areas with the highest STD cases or rates. The sample was stratified by jurisdiction population size. We examined the primary referral clinics for STDs, the services offered and the impact of budget cuts (limited to government funding only). Data were analyzed using SAS, and analyses were weighted for nonresponse.
Twenty-two percent of LHDs cited a specialty STD clinic as their primary referral for STD services; this increased to 53.5% of LHDs when combination STD-family planning clinics were included. The majority of LHDs (62.8%) referred to clinics providing same-day services. Sexually transmitted disease clinics more frequently offered extragenital testing for chlamydia and/or gonorrhea (74.7%) and gonorrhea culture (68.5%) than other clinics (52.9%, 46.2%, respectively; P < 0.05). The majority of LHDs (61.5%) reported recent budget cuts. Of those with decreased budgets, the most common impacts were fewer clinic hours (42.8%; 95% confidence interval CI, 24.4-61.2), reduced routine screening (40.2%; 95% CI, 21.7-58.8) and reductions in partner services (42.1%; 95% CI, 23.6-60.7). One quarter of those with reduced STD budgets increased fees or copays for clients.
Findings demonstrate gaps and reductions in US public STD services including clinical services that play an important role in reducing disease transmission. Furthermore, STD clinics tended to offer more specialized STD services than other public clinics.
After nearly three decades of “ICT for development”, the rollout of ICT backbone infrastructure remains challenging throughout Africa. African states do not only depend on the technology of foreign ...companies but must also seek external finance to pay for it. This dual dependency puts African governments in a vulnerable position, leading us to inquire: to what extent does the dual dependency on foreign finance and technology affect African agency in ICT infrastructure provider choice? The paper proposes a model that distinguishes between the agency of higher and lower income countries. Elaborating on the latter, the model assumes that the source of foreign ICT-related finance (i.e., China, World Bank, both, internal) determines whether the recipient state can exercise a weak, medium, or strong degree of agency in its ICT infrastructure provider choice. The paper further argues that the link between foreign finance and degree of agency is shaped by the digital development agenda of the donor. For instance, the model predicts that countries which predominantly received Chinese ICT finance possess weak agency when choosing an ICT infrastructure provider because China's digital development agenda ties the provision of finance to hiring a Chinese contractor. By examining the ICT-related financial inflows and geographical distribution of network equipment providers in African states, the paper shows that the source of finance affects the degree of agency and, subsequently, the choice of ICT infrastructure provider. However, the analysis also suggests a divide in African agency along former colonial lines. In fact, the model holds only for countries without colonial ties to France whereas former French colonies all contracted Huawei, regardless of ICT finance flows.
•Proposes a model for African agency in choice of network equipment provider.•Development finance determines African agency in ICT infrastructure provider choice.•Digital development agendas of donors affect ICT infrastructure provider choice.•Geospatial mapping of fiber-optic cables sets Francophone states apart from others.
Over the past few decades, China emerged as Africa's main partner in digital development. Sino-African cooperation in the Information and Communications Technology (ICT) sector meets African demand ...for advanced technologies and know-how while helping China to position itself in the global ICT sector. Albeit crucial for Africa's digital development in the short term, this paper argues that the breadth of Sino-African cooperation carries important long-term consequences that could afford China latent control over Africa's digital development. Drawing on Susan Strange's pillars of structural power, this paper considers how the rollout of fiber-optic network cables underpins Chinese control over production, how the construction of data centers might impinge on security, and how research partnerships enhance norms and standards in future innovation-the knowledge pillar. The paper argues that the enabling force of Sino-African cooperation in these three realms is Chinese finance. To test this claim, I conduct a Qualitative Comparative Analysis (QCA) of 42 states in Sub-Saharan Africa, showing that Chinese aid and, to a lesser extent, Chinese loans are the main drivers of Sino-African ties in the ICT sector. The paper concludes that Chinese financial support not only promotes Africa's digital development but also paves the way to Chinese structural power in the ICT sector.
Poly ADP-ribose polymerase inhibitors (PARPi) have transformed ovarian cancer (OC) treatment, primarily for tumours deficient in homologous recombination repair. Combining VEGF-signalling inhibitors ...with PARPi has enhanced clinical benefit in OC. To study drivers of efficacy when combining PARP inhibition and VEGF-signalling, a cohort of patient-derived ovarian cancer xenografts (OC-PDXs), representative of the molecular characteristics and drug sensitivity of patient tumours, were treated with the PARPi olaparib and the VEGFR inhibitor cediranib at clinically relevant doses. The combination showed broad anti-tumour activity, reducing growth of all OC-PDXs, regardless of the homologous recombination repair (HRR) mutational status, with greater additive combination benefit in tumours poorly sensitive to platinum and olaparib. In orthotopic models, the combined treatment reduced tumour dissemination in the peritoneal cavity and prolonged survival. Enhanced combination benefit was independent of tumour cell expression of receptor tyrosine kinases targeted by cediranib, and not associated with change in expression of genes associated with DNA repair machinery. However, the combination of cediranib with olaparib was effective in reducing tumour vasculature in all the OC-PDXs. Collectively our data suggest that olaparib and cediranib act through complementary mechanisms affecting tumour cells and tumour microenvironment, respectively. This detailed analysis of the combined effect of VEGF-signalling and PARP inhibitors in OC-PDXs suggest that despite broad activity, there is no dominant common mechanistic inter-dependency driving therapeutic benefit.
Accurate estimation of hyperopia and astigmatism is challenging in delayed children. Conventional skiascopy holds rows of increasing power ± lenses vertically in front of one eye. The school bus ...accommodation-relaxing skiascopy (SBA-RS) design holds child-friendly, lenses +1 to +10D horizontally so that a higher power fogs the nontested eye-relaxing accommodation without cycloplegia.
Design: Evaluation of diagnostic test. Subjects: Patients undergoing comprehensive eye examination in a pediatric ophthalmology practice. Cycloplegic (cyclopentolate 1%) retinoscopy was compared to dry SBA-RS and Retinomax (Righton, Japan) during pediatric eye examinations. Outcome measures: correlations, Chi-square and receiver operating characteristic (ROC) curve.
Of 470 patients with a median age 6 years, 238 were under the age of 60 months and 110 had developmental delays. For those with cycloplegic spherical equivalent hyperopia over 0.7 D, median (90% CI) value for retinoscopy was +2.63 D (+0.75, +6.88), for SBA-RS was +2.50 D (+0.50, +6.75) and less for 184 with Retinomax +1.88 D (-1.56, +6.13) but similar despite delays. Astigmatic cylinder SBA-RS +1.50 D (+0.25, +4.00) lagged retinoscopy +1.75 D (+0.75,+4.50) but Retinomax was greater +2.00 D (+0.25, +4.64). Cycloplegic refractive components such as spherical equivalent, cylinder, and J0 and J45 power vectors correlated highly and were near unity with SBA-RS and Retinomax with the latter deviating greater. SBA-RS screened for amblyopia risk factors up to 92% sensitive and 94% specific.
Accommodation-relaxing horizontal skiascopy very precisely estimates astigmatism power and axis and only lags cycloplegic refraction by about 0.15D in hyperopic patients fairly independent of neurodevelopmental delay. This technique can quickly estimate refraction even in delayed patients potentially reducing some need for cycloplegia.
NCT03668067.
Handheld devices can automatically give an estimate of refraction. The established method for refraction comparison using spherical equivalent (M) and J0, J45 vector transformations by Bland-Altman ...analysis is too complex for non-eye doctors involved with vision screening and remote vision clinics. Therefore, a simpler comparison technique was developed.
Based on the spectacle limit to resolve grade A 1 logMAR, B 3 logMAR and C 6 logMAR blur, J0, J45, and M are combined into the Alaska Blind Child Discovery (ABCD) composite ellipsoid GRADE system. Pediatric eye patients had confirmatory examination after dry refraction with three portable autorefractors: Plusoptix, 2WIN and Retinomax. The refractions were then compared using both Bland-Altman and ABCD composite. Performance to detect AAPOS amblyopia risk factors was also assessed.
A total of 202 children, mean age seven years, 28% high spectacle need and 43% AAPOS 2013 amblyopia risk factors showed high correlation with cycloplegic refraction (intraclass correlation 0.49 to 0.90) for sphere, J0 and J45 spectacle components. Plusoptix had more (10%) inconclusives due to patients out-of-range. The Retinomax was unable to screen some younger children and was less reliable for sphere but gave more precise astigmatism estimates. The proportion of autorefractions expected to give GRADE A/B high-need patients acuity improvement to 20/40 would be 41% for Plusoptix, 39% for 2WIN and 65% for Retinomax. Sensitivity/specificity for amblyopia risk factor detection was 80%/83% for Plusoptix, 72%/88% for 2WIN and 84%/73% for Retinomax.
The simplified spectacle comparison resembled Bland-Altman and could assist lay vision screeners and non-eye doctors attempting remote spectacle donation worldwide.
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