I am an MD/PhD (Epidemiology) candidate, infectious diseases epidemiologist, and global health policy scientist. My work draws upon diverse quantitative methodologies to inform policy in global infectious diseases.
Honors & Awards
Media coverage, New York Times, BBC, The Guardian, NPR, San Francisco Chronicle, Scientific American, NBC News
Top 5 articles of 2017, JAMA Pediatrics (2017)
Medical Scientist Training Program (MSTP), National Institutes of Health (NIH) (2016)
Kass Award, Infectious Diseases Society of America (2016)
Clinical Research Mentorship (CRM) grantee, Doris Duke Charitable Foundation (2015)
Medical Scholar, Infectious Diseases Society of America (2015)
Benjamin H. Kean Fellow, American Society of Tropical Medicine and Hygiene (2015)
Young Investigator Award, Conference on Retroviruses and Opportunistic Infections (2015)
Student/Post-Doc Travel Award, American Society of Tropical Medicine and Hygiene (2014)
Outstanding Senior, Rice University Department of Bioengineering (2013)
Professional Affiliations and Activities
Member, American Society of Tropical Medicine and Hygiene (2015 - Present)
Member, Infectious Diseases Society of America (2015 - Present)
Education & Certifications
Bachelor of Science, Rice University, Bioengineering (2013)
Typhoid conjugate vaccines: a new tool in the fight against antimicrobial resistance.
The Lancet. Infectious diseases
Typhoid fever is an acute systemic infectious disease responsible for an estimated 12-20 million illnesses and over 150 000 deaths annually. In March, 2018, a new recommendation was issued by WHO for the programmatic use of typhoid conjugate vaccines in endemic countries. Health economic analyses of typhoid vaccines have informed funding decisions and national policies regarding vaccine rollout. However, by focusing only on averted typhoid cases and their associated costs, traditional cost-effectiveness analyses might underestimate crucial benefits of typhoid vaccination programmes, because the potential effect of typhoid vaccines on the treatment of patients with non-specific acute febrile illnesses is not considered. For every true case of typhoid fever, three to 25 patients without typhoid disease are treated with antimicrobials unnecessarily, conservatively amounting to more than 50 million prescriptions per year. Antimicrobials for suspected typhoid might therefore be an important selective pressure for the emergence and spread of antimicrobial resistance globally. We propose that large-scale, more aggressive typhoid vaccination programmes-including catch-up campaigns in children up to 15 years of age, and vaccination in lower incidence settings-have the potential to reduce the overuse of antimicrobials and thereby reduce antimicrobial resistance in many bacterial pathogens. Funding bodies and national governments must therefore consider the potential for broad reductions in antimicrobial use and resistance in decisions related to the rollout of typhoid conjugate vaccines.
View details for DOI 10.1016/S1473-3099(18)30350-5
View details for PubMedID 30170987
Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.
Proceedings of the National Academy of Sciences of the United States of America
Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA.
View details for DOI 10.1073/pnas.1708729114
View details for PubMedID 29301964
Comparison of Strategies and Incidence Thresholds for Vi Conjugate Vaccines Against Typhoid Fever: A Cost-effectiveness Modeling Study.
The Journal of infectious diseases
Typhoid fever remains a major public health problem globally. While new Vi conjugate vaccines hold promise for averting disease, the optimal programmatic delivery remains unclear. We aimed to identify the strategies and associated epidemiologic conditions under which Vi conjugate vaccines would be cost-effective.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulated multiple vaccination strategies with a typhoid Vi conjugate vaccine from a societal perspective. We simulated 10-year vaccination programs with (1) routine immunization of infants (aged <1 year) through the Expanded Program on Immunization (EPI) and (2) routine immunization of infants through the EPI plus a 1-time catch-up campaign in school-aged children (aged 5-14 years). In the base case analysis, we assumed a 0.5% case-fatality rate for all cases of clinically symptomatic typhoid fever and defined strategies as highly cost-effective by using the definition of a low-income country (defined as a country with a gross domestic product of $1045 per capita). We defined incidence as the true number of clinically symptomatic people in the population per year.Vi conjugate typhoid vaccines were highly cost-effective when administered by routine immunization activities through the EPI in settings with an annual incidence of >50 cases/100000 (95% uncertainty interval, 40-75 cases) and when administered through the EPI plus a catch-up campaign in settings with an annual incidence of >130 cases/100000 (95% uncertainty interval, 50-395 cases). The incidence threshold was sensitive to the typhoid-related case-fatality rate, carrier contribution to transmission, vaccine characteristics, and country-specific economic threshold for cost-effectiveness.Typhoid Vi conjugate vaccines would be highly cost-effective in low-income countries in settings of moderate typhoid incidence (50 cases/100000 annually). These results were sensitive to case-fatality rates, underscoring the need to consider factors contributing to typhoid mortality (eg, healthcare access and antimicrobial resistance) in the global vaccination strategy.
View details for DOI 10.1093/infdis/jix598
View details for PubMedID 29444257
- The Perils of Trumping Science in Global Health - The Mexico City Policy and Beyond. New England journal of medicine 2017
A call to strengthen the global strategy against schistosomiasis and soil-transmitted helminthiasis: the time is now.
The Lancet. Infectious diseases
2017; 17 (2): e64-e69
In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis.
View details for DOI 10.1016/S1473-3099(16)30535-7
View details for PubMedID 27914852
View details for PubMedCentralID PMC5280090
Public Health and Economic Consequences of Vaccine Hesitancy for Measles in the United States.
Routine childhood vaccination is declining in some regions of the United States due to vaccine hesitancy, which risks the resurgence of many infectious diseases with public health and economic consequences. There are ongoing policy debates on the state and national level, including legislation around nonmedical (personal-belief) exemptions for childhood vaccination and possibly a special government commission on vaccine safety, which may affect vaccine coverage.To estimate the number of measles cases in US children and the associated economic costs under scenarios of different levels of vaccine hesitancy, using the case example of measles, mumps, and rubella (MMR) vaccination and measles.Publicly available data from the US Centers for Disease Control and Prevention were used to simulate county-level MMR vaccination coverage in children (age 2-11 years) in the United States. A stochastic mathematical model was adapted for infectious disease transmission that estimated a distribution for outbreak size as it relates to vaccine coverage. Economic costs per measles case were obtained from the literature. The predicted effects of increasing the prevalence of vaccine hesitancy as well as the removal of nonmedical exemptions were estimated. The model was calibrated to annual measles cases in US children over recent years, and the model prediction was validated using an independent data set from England and Wales.Annual measles cases in the United States and the associated public sector costs.A 5% decline in MMR vaccine coverage in the United States would result in an estimated 3-fold increase in measles cases for children aged 2 to 11 years nationally every year, with an additional $2.1 million in public sector costs. The numbers would be substantially higher if unvaccinated infants, adolescents, and adult populations were also considered. There was variation around these estimates due to the stochastic elements of measles importation and sensitivity of some model inputs, although the trend was robust.This analysis predicts that even minor reductions in childhood vaccination, driven by vaccine hesitancy (nonmedical and personal belief exemptions), will have substantial public health and economic consequences. The results support an urgent need to address vaccine hesitancy in policy dialogues at the state and national level, with consideration of removing personal belief exemptions of childhood vaccination.
View details for DOI 10.1001/jamapediatrics.2017.1695
View details for PubMedID 28738137
Assessment of global guidelines for preventive chemotherapy against schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study
LANCET INFECTIOUS DISEASES
2016; 16 (9): 1065-1075
WHO guidelines recommend annual treatment for schistosomiasis or soil-transmitted helminthiasis when prevalence in school-aged children is at or above a threshold of 50% and 20%, respectively. Separate treatment guidelines are used for these two helminthiases, and integrated community-wide treatment is not recommended. We assessed the cost-effectiveness of changing prevalence thresholds and treatment guidelines under an integrated delivery framework.We developed a dynamic, age-structured transmission and cost-effectiveness model that simulates integrated preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis. We assessed a 5-year treatment programme with praziquantel (40 mg/kg per treatment) against schistosomiasis and albendazole (400 mg per treatment) against soil-transmitted helminthiasis at 75% coverage. We defined strategies as highly cost-effective if the incremental cost-effectiveness ratio was less than the World Bank classification for a low-income country (gross domestic product of US$1045 per capita). We calculated the prevalence thresholds for cost-effective preventive chemotherapy of various strategies, and estimated treatment needs for sub-Saharan Africa.Annual preventive chemotherapy against schistosomiasis was highly cost-effective in treatment of school-aged children at a prevalence threshold of 5% (95% uncertainty interval [UI] 1·7-5·2; current guidelines recommend treatment at 50% prevalence) and for community-wide treatment at a prevalence of 15% (7·3-18·5; current recommendation is unclear, some community treatment recommended at 50% prevalence). Annual preventive chemotherapy against soil-transmitted helminthiasis was highly cost-effective in treatment of school-aged children at a prevalence of 20% (95% UI 5·4-30·5; current guidelines recommend treatment at 20% prevalence) and the entire community at 60% (35·3-85·1; no guidelines available). When both helminthiases were co-endemic, prevalence thresholds using integrated delivery were lower. Using this revised treatment framework, we estimated that treatment needs would be six times higher than WHO guidelines for praziquantel and two times higher for albendazole. An additional 21·3% (95% Bayesian credible interval 20·4-22·2) of the population changed from receiving non-integrated treatment under WHO guidelines to integrated treatment (both praziquantel and albendazole). Country-specific economic differences resulted in heterogeneity around these prevalence thresholds.Annual preventive chemotherapy programmes against schistosomiasis and soil-transmitted helminthiasis are likely to be highly cost-effective at prevalences lower than WHO recommendations. These findings support substantial treatment scale-up, community-wide coverage, integrated treatment in co-endemic settings that yield substantial cost synergies, and country-specific treatment guidelines.Doris Duke Charitable Foundation, Mount Sinai Hospital-University Health Network AMO Innovation Fund, and Stanford University Medical Scholars Programme.
View details for DOI 10.1016/S1473-3099(16)30073-1
View details for Web of Science ID 000381655200036
View details for PubMedID 27286968
Abstinence Funding Was Not Associated With Reductions In HIV Risk Behavior In Sub-Saharan Africa
2016; 35 (5): 856-863
The President's Emergency Plan for AIDS Relief (PEPFAR) has been the largest funder of abstinence and faithfulness programming in sub-Saharan Africa, with a cumulative investment of over US $1.4 billion in the period 2004-13. We examined whether PEPFAR funding for abstinence and faithfulness programs, which aimed to reduce the risk of HIV transmission, was associated with a relative change in five outcomes indicative of high-risk sexual behavior: number of sexual partners in the past twelve months for men and for women, age at first sexual intercourse for men and for women, and teenage pregnancies. Using nationally representative surveys from twenty-two sub-Saharan African countries, we compared trends between people living in countries that received PEPFAR abstinence and faithfulness funding and those living in countries that did not in the period 1998-2013. We found no evidence to suggest that PEPFAR funding was associated with population-level reductions in any of the five outcomes. These results suggest that alternative funding priorities for HIV prevention may yield greater health benefits.
View details for DOI 10.1377/hlthaff.2015.0828
View details for Web of Science ID 000375796700015
View details for PubMedID 27140992
Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study.
The Lancet. Global health
2015; 3 (10): e629-38
More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire.We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted.Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities.Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment.Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund.
View details for DOI 10.1016/S2214-109X(15)00047-9
View details for PubMedID 26385302
- Review of the 2017 WHO Guideline: Preventive chemotherapy to control soil-transmitted helminth infections in at-risk population groups. An opportunity lost in translation. PLoS neglected tropical diseases 2018; 12 (4): e0006296
Deworming in pre-school age children: A global empirical analysis of health outcomes.
PLoS neglected tropical diseases
2018; 12 (5): e0006500
There is debate over the effectiveness of deworming children against soil-transmitted helminthiasis (STH) to improve health outcomes, and current evidence may be limited in study design and generalizability. However, programmatic deworming continues throughout low and middle-income countries.We performed an empirical evaluation of the relationship between deworming in pre-school age children (ages 1-4 years) within the previous 6 months, as proxy-reported by the mother, and health outcomes of weight, height, and hemoglobin. We used nationally representative cross-sectional data from 45 countries using the Demographic and Health Surveys (DHS) during the period 2005-2016. We used logistic regression with coarsened exact matching, fixed effects for survey and year, and person-level covariates. We included data on 325,115 children in 45 STH-endemic countries from 66 DHS surveys. Globally in STH-endemic countries, children who received deworming treatment were less likely to be stunted (1.2 percentage point decline from mean of 36%; 95% CI [-1.9, -0.5%]; p<0.001), but we did not detect consistent associations between deworming and anemia or weight. In sub-Saharan Africa, we found that children who received deworming treatment were less likely to be stunted (1.1 percentage point decline from mean of 36%; 95% CI [-2.1, -0.2%]; p = 0.01) and less likely to have anemia (1.8 percentage point decline from mean of 58%; 95% CI [-2.8, -0.7%]; p<0.001), but we did not detect consistent associations between deworming and weight. These findings were robust across multiple statistical models, and we did not find consistently measurable associations with data from non-endemic settings.Among pre-school age children, we detected a robust and consistent association between deworming and reduced stunting, with additional evidence for reduced anemia in sub-Saharan Africa. We did not find a consistent relationship between deworming and improved weight. This global empirical analysis provides evidence to support the deworming of pre-school age children.
View details for DOI 10.1371/journal.pntd.0006500
View details for PubMedID 29852012
The human-snail transmission environment shapes long term schistosomiasis control outcomes: Implications for improving the accuracy of predictive modeling.
PLoS neglected tropical diseases
2018; 12 (5): e0006514
Schistosomiasis is a chronic parasitic trematode disease that affects over 240 million people worldwide. The Schistosoma lifecycle is complex, involving transmission via specific intermediate-host freshwater snails. Predictive mathematical models of Schistosoma transmission have often chosen to simplify or ignore the details of environmental human-snail interaction in their analyses. Schistosome transmission models now aim to provide better precision for policy planning of elimination of transmission. This heightens the importance of including the environmental complexity of vector-pathogen interaction in order to make more accurate projections.We propose a nonlinear snail force of infection (FOI) that takes into account an intermediate larval stage (miracidium) and snail biology. We focused, in particular, on the effects of snail force of infection (FOI) on the impact of mass drug administration (MDA) in human communities. The proposed (modified) model was compared to a conventional model in terms of their predictions. A longitudinal dataset generated in Kenya field studies was used for model calibration and validation. For each sample community, we calibrated modified and conventional model systems, then used them to model outcomes for a range of MDA regimens. In most cases, the modified model predicted more vigorous post-MDA rebound, with faster relapse to baseline levels of infection. The effect was pronounced in higher risk communities. When compared to observed data, only the modified system was able to successfully predict persistent rebound of Schistosoma infection.The observed impact of varying location-specific snail inputs sheds light on the diverse MDA response patterns noted in operational research on schistosomiasis control, such as the recent SCORE project. Efficiency of human-to-snail transmission is likely to be much higher than predicted by standard models, which, in practice, will make local elimination by implementation of MDA alone highly unlikely, even over a multi-decade period.
View details for DOI 10.1371/journal.pntd.0006514
View details for PubMedID 29782500
Invasive Pomacea snails as important intermediate hosts of Angiostrongylus cantonensis in Laos, Cambodia and Vietnam: implications for outbreaks of eosinophilic meningitis.
The rat lungworm Angiostrongylus cantonensis causes human eosinophilic meningitis and it is endemic in Southeast Asia, but little is known about its distribution in Laos, Cambodia and Vietnam. We conducted a multi-country survey for A. cantonensis in these countries to estimate its prevalence in snails along the Mekong River and the east coast of Vietnam. We identified Angiostrongylus species by morphological and molecular analysis. We found A. cantonensis in the invasive snail, Pomacea spp. The wide accessibility of Pomacea snails, along with their infection by A. cantonensis, indicates that this snail species could be used in surveillance for preventing outbreaks of eosinophilic meningitis.
View details for DOI 10.1016/j.actatropica.2018.03.021
View details for PubMedID 29574000
Mobile phone and handheld microscopes for public health applications
LANCET PUBLIC HEALTH
2017; 2 (8): E355
View details for Web of Science ID 000425587900010
- Mobile-phone and handheld microscopy for neglected tropical diseases. PLoS neglected tropical diseases 2017; 11 (7): e0005550
Schistosoma haematobium Egg Excretion does not Increase after Exercise: Implications for Diagnostic Testing.
The American journal of tropical medicine and hygiene
Children are frequently invited to exercise before micturition, as it is believed that this will result in higher Schistosoma haematobium egg excretion, and hence, increases sensitivity of microscopic diagnoses. However, the evidence of this recommendation is scant. In the study presented here, 257 children, aged 2-15 years from south Côte d'Ivoire, provided urine samples for microscopy on consecutive days; one sample without prior exercise and one sample after exercise. Comparing the same individuals without and with prior exercise, sample positivity for S. haematobium (25.7% versus 23.0%, P = 0.31) and mean egg counts (10.2 eggs/10 mL versus 8.5 eggs/10 mL, P = 0.45) did not differ. Exercise before urine collection does not appear to increase S. haematobium egg excretion.
View details for DOI 10.4269/ajtmh.17-0728
View details for PubMedID 29260647
- Comparison of sensitivity and faecal egg counts of Mini-FLOTAC using fixed stool samples and Kato-Katz technique for the diagnosis of Schistosoma mansoni and soil-transmitted helminths ACTA TROPICA 2016; 164: 107-116
Evaluation of a Urine Pooling Strategy for the Rapid and Cost-Efficient Prevalence Classification of Schistosomiasis.
PLoS neglected tropical diseases
2016; 10 (8)
A key epidemiologic feature of schistosomiasis is its focal distribution, which has important implications for the spatial targeting of preventive chemotherapy programs. We evaluated the diagnostic accuracy of a urine pooling strategy using a point-of-care circulating cathodic antigen (POC-CCA) cassette test for detection of Schistosoma mansoni, and employed simulation modeling to test the classification accuracy and efficiency of this strategy in determining where preventive chemotherapy is needed in low-endemicity settings.We performed a cross-sectional study involving 114 children aged 6-15 years in six neighborhoods in Azaguié Ahoua, south Côte d'Ivoire to characterize the sensitivity and specificity of the POC-CCA cassette test with urine samples that were tested individually and in pools of 4, 8, and 12. We used a Bayesian latent class model to estimate test characteristics for individual POC-CCA and quadruplicate Kato-Katz thick smears on stool samples. We then developed a microsimulation model and used lot quality assurance sampling to test the performance, number of tests, and total cost per school for each pooled testing strategy to predict the binary need for school-based preventive chemotherapy using a 10% prevalence threshold for treatment.The sensitivity of the urine pooling strategy for S. mansoni diagnosis using pool sizes of 4, 8, and 12 was 85.9%, 79.5%, and 65.4%, respectively, when POC-CCA trace results were considered positive, and 61.5%, 47.4%, and 30.8% when POC-CCA trace results were considered negative. The modeled specificity ranged from 94.0-97.7% for the urine pooling strategies (when POC-CCA trace results were considered negative). The urine pooling strategy, regardless of the pool size, gave comparable and often superior classification performance to stool microscopy for the same number of tests. The urine pooling strategy with a pool size of 4 reduced the number of tests and total cost compared to classical stool microscopy.This study introduces a method for rapid and efficient S. mansoni prevalence estimation through examining pooled urine samples with POC-CCA as an alternative to widely used stool microscopy.
View details for DOI 10.1371/journal.pntd.0004894
View details for PubMedID 27504954
View details for PubMedCentralID PMC4978437
- Cost-effectiveness of community-wide treatment for helminthiasis--Authors' reply. The Lancet. Global health 2016; 4 (3): e157-8
- Improving helminth treatment access: costs and opportunities. The Lancet. Infectious diseases 2016; 16 (7): 762–64
Strategies for last mile implementation of global health technologies
The Lancet. Global health
2014; 2 (9): e497-8
View details for DOI 10.1016/S2214-109X(14)70253-0
Interaction of Shiga Toxin with the A-domains and Multimers of von Willebrand Factor
JOURNAL OF BIOLOGICAL CHEMISTRY
2013; 288 (46): 33118-33123
Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli causes diarrhea-associated hemolytic-uremic syndrome (DHUS), a severe renal thrombotic microangiopathy. We investigated the interaction between Stx and von Willebrand Factor (VWF), a multimeric plasma glycoprotein that mediates platelet adhesion, activation, and aggregation. Stx bound to ultra-large VWF (ULVWF) secreted from and anchored to stimulated human umbilical vein endothelial cells, as well as to immobilized VWF-rich human umbilical vein endothelial cell supernatant. This Stx binding was localized to the A1 and A2 domain of VWF monomeric subunits and reduced the rate of ADAMTS-13-mediated cleavage of the Tyr(1605)-Met(1606) peptide bond in the A2 domain. Stx-VWF interaction and the associated delay in ADAMTS-13-mediated cleavage of VWF may contribute to the pathophysiology of DHUS.
View details for DOI 10.1074/jbc.M113.487413
View details for Web of Science ID 000328841700027
View details for PubMedID 24097977
View details for PubMedCentralID PMC3829160
The Aging of Biomedical Research in the United States
2011; 6 (12)
In the past 30 years, the average age of biomedical researchers has steadily increased. The average age of an investigator at the National Institutes of Health (NIH) rose from 39 to 51 between 1980 and 2008. The aging of the biomedical workforce was even more apparent when looking at first-time NIH grantees. The average age of a new investigator was 42 in 2008, compared to 36 in 1980. To determine if the rising barriers at NIH for entry in biomedical research might impact innovative ideas and research, we analyzed the research and publications of Nobel Prize winners from 1980 to 2010 to assess the age at which their pioneering research occurred. We established that in the 30-year period, 96 scientists won the Nobel Prize in medicine or chemistry for work related to biomedicine, and that their groundbreaking research was conducted at an average age of 41-one year younger than the average age of a new investigator at NIH. Furthermore, 78% of the Nobel Prize winners conducted their research before the age of 51, the average age of an NIH principal investigator. This suggested that limited access to NIH might inhibit research potential and novel projects, and could impact biomedicine and the next generation scientists in the United States.
View details for DOI 10.1371/journal.pone.0029738
View details for Web of Science ID 000300676300082
View details for PubMedID 22216352
View details for PubMedCentralID PMC3247288