656 research outputs found

    Viewpoint: Evaluating the impact of malaria control efforts on mortality in sub-Saharan Africa

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    OBJECTIVE To describe an approach for evaluating the impact of malaria control efforts on malaria-associated mortality in sub-Saharan Africa, where disease-specific mortality trends usually cannot be measured directly and most malaria deaths occur among young children. METHODS Methods for evaluating changes in malaria-associated mortality are examined; advantages and disadvantages are presented. RESULTS All methods require a plausibility argument - i.e., an assumption that mortality reductions can be attributed to programmatic efforts if improvements are found in steps of the causal pathway between intervention scale-up and mortality trends. As different methods provide complementary information, they can be used together. We recommend following trends in the coverage of malaria control interventions, other factors influencing childhood mortality, malaria-associated morbidity (especially anaemia), and all-cause childhood mortality. This approach reflects decreases in malaria's direct and indirect mortality burden and can be examined in nearly all countries. Adding other information can strengthen the plausibility argument: trends in indicators of malaria transmission, information from demographic surveillance systems and sentinel sites where malaria diagnostics are systematically used, and verbal autopsies linked to representative household surveys. Health facility data on malaria deaths have well-recognized limitations; however, in specific circumstances, they could produce reliable trends. Model-based predictions can help describe changes in malaria-specific burden and assist with program management and advocacy. CONCLUSIONS Despite challenges, efforts to reduce malaria-associated mortality in Africa can be evaluated with trends in malaria intervention coverage and all-cause childhood mortality. Where there are resources and interest, complementary data on malaria morbidity and malaria-specific mortality could be added

    China Studies Review

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    In our first section, we introduce three short pieces that examine important issues in U.S.-China investment relations, public opinion in China and Japan, and the Hong Kong pro-democracy move-ment. Benjamin Pollock examines the progression of negotiations between the United States and China in adopting a high-quality bilateral investment treaty. Cheng Zhang uses data from Genron to understand the reasons behind mutual dis-trust between China and Japan. Adrienne Dalton looks at the role of Hong Kong triads in the suppression of the 2014 Hong Kong pro-democracy demonstrations. Our second section features six research articles covering a wide range of topics. Jakob Bund explores U.S.-China relations in cyberspace and provides an alternative framework by which the two countries can cooperate in the absence of trust. Patrick Lozada discusses China’s “creative indus-tries”, and the shortcomings of China’s creative special economic zones in foster-ing an innovation economy. David Rubin builds upon Bruce Gilley’s spectrum of democratic and authoritarian environ-mentalism and finds that in the context of environmental policymaking, China is transitioning towards more inclusivity and grassroots engagement. Peter Kim also examines China’s environmental policy and uses dust and sandstorms, also known as “yellow dust”, to examine the challenges and opportunities for environmental coop-eration in Northeast Asia. Shuxian Luo conducts a comparative analysis of China and India’s naval modernization efforts, noting that while China’s rapid economic development has spurred its naval modern-ization at a more rapid pace, there are other important elements such as differing threat perceptions and alliance options that help to explain India’s relative lag in naval mod-ernization. Finally, Winston Kung presents a Taiwan Straits crisis scenario analysis that examines the legal, diplomatic, strategic, and domestic opinion factors that would likely affect a U.S. response, concluding that U.S. diplomatic and military leverage would eventually lead China and Taiwan to de-escalate tensions in the region

    Incompatibilities Involving Yeast Mismatch Repair Genes: A Role for Genetic Modifiers and Implications for Disease Penetrance and Variation in Genomic Mutation Rates

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    Genetic background effects underlie the penetrance of most genetically determined phenotypes, including human diseases. To explore how such effects can modify a mutant phenotype in a genetically tractable system, we examined an incompatibility involving the MLH1 and PMS1 mismatch repair genes using a large population sample of geographically and ecologically diverse Saccharomyces cerevisiae strains. The mismatch repair incompatibility segregates into naturally occurring yeast strains, with no strain bearing the deleterious combination. In assays measuring the mutator phenotype conferred by different combinations of MLH1 and PMS1 from these strains, we observed a mutator phenotype only in combinations predicted to be incompatible. Surprisingly, intragenic modifiers could be mapped that specifically altered the strength of the incompatibility over a 20-fold range. Together, these observations provide a powerful model in which to understand the basis of disease penetrance and how such genetic variation, created through mating, could result in new mutations that could be the raw material of adaptive evolution in yeast populations

    The albino locus and locomotor behavior in the mouse: Studies using extended test intervals

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    The influence of albinism upon initial activity in novel surroundings was examined using coisogenic and congenic lines of mice. In comparison with those of previous studies, an extended test interval was used, and this modification produced significant main and interaction effects of the c locus upon activity for both lines. The present findings confirm and extend those of previous studies upon the depressant effects of albinism based upon coisogenic lines, and extend the findings to congenic lines as well.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44104/1/10519_2005_Article_BF01065627.pd

    Testing, stretching, and aligning:Using ‘ironic personae’ to make sense of complicated issues

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    Irony and humor play an important role in both organizing and organizations, because they both help to collide and contrast ideas as well as mitigate and moderate criticism. Our empirical observations of a senior management team suggest participants frequently use verbal irony and aggressive conversational humor through ‘ironic personae’ – a cast of characters, real or imaginary – as a vehicle for pragmatically making sense of complicated topics. We show how ironic personae perform three functions: (i) testing new positions on topics in a non-committal way; (ii) stretching the frame of comparison of a group; and (iii) aligning shared understanding and commitment. Thus, our analysis sheds light on an underexplored and undertheorised pragmatic vehicle for the expression of humorous verbal irony and aggressive conversational humor

    Knockdown of Midgut Genes by dsRNA-Transgenic Plant-Mediated RNA Interference in the Hemipteran Insect Nilaparvata lugens

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    BACKGROUND: RNA interference (RNAi) is a powerful technique for functional genomics research in insects. Transgenic plants producing double-stranded RNA (dsRNA) directed against insect genes have been reported for lepidopteran and coleopteran insects, showing potential for field-level control of insect pests, but this has not been reported for other insect orders. METHODOLOGY/PRINCIPAL FINDINGS: The Hemipteran insect brown planthopper (Nilaparvata lugens Stål) is a typical phloem sap feeder specific to rice (Oryza sativa L.). To analyze the potential of exploiting RNAi-mediated effects in this insect, we identified genes (Nlsid-1 and Nlaub) encoding proteins that might be involved in the RNAi pathway in N. lugens. Both genes are expressed ubiquitously in nymphs and adult insects. Three genes (the hexose transporter gene NlHT1, the carboxypeptidase gene Nlcar and the trypsin-like serine protease gene Nltry) that are highly expressed in the N. lugens midgut were isolated and used to develop dsRNA constructs for transforming rice. RNA blot analysis showed that the dsRNAs were transcribed and some of them were processed to siRNAs in the transgenic lines. When nymphs were fed on rice plants expressing dsRNA, levels of transcripts of the targeted genes in the midgut were reduced; however, lethal phenotypic effects after dsRNA feeding were not observed. CONCLUSIONS: Our study shows that genes for the RNAi pathway (Nlsid-1 and Nlaub) are present in N. lugens. When insects were fed on rice plant materials expressing dsRNAs, RNA interference was triggered and the target genes transcript levels were suppressed. The gene knockdown technique described here may prove to be a valuable tool for further investigations in N. lugens. The results demonstrate the potential of dsRNA-mediated RNAi for field-level control of planthoppers, but appropriate target genes must be selected when designing the dsRNA-transgenic plants

    HER2 expression as a potential marker for response to therapy targeted to the EGFR

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    Since human epidermal growth factor receptor 2 (HER2) is known to participate with the epidermal growth factor receptor (EGFR) in mitogenic signalling, we hypothesised that HER2 overexpression might indicate responsiveness to EGFR targeted therapies. MCF7 breast cancer cells transfected with the HER2 gene were subcloned to establish a set of genetically related cell lines expressing graded levels of HER2 by immunoblot analysis. The subcloned cell lines and parental MCF7 cells were characterised by their growth characteristics, and cell by cell patterns of EGFR, HER2 and HER3 expression as well as levels of phosphorylated mitogen-activated protein kinase (MAPK) and AKT by laser scanning cytometry (LSC). Growth inhibition assays were used to characterise response to EGFR targeted therapy, and to determine the relationship between therapeutic response and levels of tyrosine kinase expression. The levels of growth inhibition of AG1478 and of the AG1478-trastuzumab combinations were correlated with levels of HER2 expression among the different cell lines. Among EGFR, HER2 and HER3, HER2 overexpression was the best single predictive marker, but combinations of two markers provided additional predictive information

    HIV-1 drug resistance mutations emerging on darunavir therapy in PI-naive and -experienced patients in the UK

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    \ua9 The Author 2016. Background: Darunavir is considered to have a high genetic barrier to resistance. Most darunavir-associated drug resistance mutations (DRMs) have been identified through correlation of baseline genotype with virological response in clinical trials. However, there is little information on DRMs that are directly selected by darunavir in clinical settings. Objectives: We examined darunavir DRMs emerging in clinical practice in the UK. Patients and methods: Baseline and post-exposure protease genotypes were compared for individuals in the UK Collaborative HIV Cohort Study who had received darunavir; analyses were stratified for PI history. A selection analysis was used to compare the evolution of subtype B proteases in darunavir recipients and matched PInaive controls. Results: Of 6918 people who had received darunavir, 386 had resistance tests pre- and post-exposure. Overall, 2.8% (11/386) of these participants developed emergent darunavir DRMs. The prevalence of baseline DRMs was 1.0% (2/198) among PI-naive participants and 13.8% (26/188) among PI-experienced participants. Emergent DRMs developed in 2.0% of the PI-naive group (4 mutations) and 3.7% of the PI-experienced group (12 mutations). Codon 77 was positively selected in the PI-naive darunavir cases, but not in the control group. Conclusions: Our findings suggest that although emergent darunavir resistance is rare, it may be more common among PI-experienced patients than those who are PI-naive. Further investigation is required to explore whether codon 77 is a novel site involved in darunavir susceptibility
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