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The health and economic benefits of the global programme to eliminate lymphatic filariasis (2000–2014)

Infectious Diseases of Poverty 2016年第1期5卷 453-471页

作者： hugo c.Turner Alison A.Bettis Brian K.chu Deborah A.McFarland Pamela J.hooper eric A.Ottesen Mark h.Bradley London centre for Neglected Tropical Disease Research LondonUK Department of Infectious Disease Epidemiology School of Public HealthFaculty of MedicineSt Marys CampusImperial College LondonNorfolk PlaceLondon W21PGUK Neglected Tropical Diseases Support center Task Force for Global HealthDecaturGAUSA Rollins School of Public health Emory UniversityAtlantaGAUSA. Global health Programs GlaxoSmithKlineLondonUK

Background:Lymphatic filariasis(LF),also known as elephantiasis,is a neglected tropical disease(NTD)targeted for elimination through a Global Programme to Eliminate LF(GPELF).Between 2000 and 2014,the GPELF has delivered 5.6 billion treatments to over 763 million people.Updating the estimated health and economic benefits of this significant achievement is important in justifying the resources and investment needed for eliminating LF.Method:We combined previously established models to estimate the number of clinical manifestations and disability-adjusted life years(DALYs)averted from three benefit cohorts(those protected from acquiring infection,those with subclinical morbidity prevented from progressing and those with clinical disease alleviated).The economic savings associated with this disease prevention was then analysed in the context of prevented medical expenses incurred by LF clinical patients,potential income loss through lost-labour,and prevented costs to the health system to care for affected individuals.The indirect cost estimates were calculated using the human capital approach.A combination of four wage sources was used to estimate the fair market value of time for an agricultural worker with LF infection(to ensure a conservative estimate,the lowest wage value was used).Results:We projected that due to the first 15 years of the GPELF 36 million clinical cases and 175(116–250)million DALYs will potentially be averted.It was estimated that due to this notable health impact,US$100.5 billion will potentially be saved over the lifetimes of the benefit cohorts.This total amount results from summing the medical expenses incurred by LF patients(US$3 billion),potential income loss(US$94 billion),and costs to the health system(US$3.5 billion)that were projected to be prevented.The results were subjected to sensitivity analysis and were most sensitive to the assumed percentage of work hours lost for those suffering from chronic disease(changing the total economic benefit between US$69.30–150.7 billion).conclusi

关键词： Lymphatic filariasis DALYs averted health impact Economic impact GPELF Programme evaluation

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Thiopurines are negatively associated with anthropometric parameters in pediatric crohn's disease

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World Journal of Gastroenterology 2018年第18期24卷 2036-2046页

作者： Neera Gupta Robert h Lustig cewin chao eric Vittinghoff howard Andrews cheng-Shiun Leu Division of Gastroenterology and Nutrition Department of Pediatrics Weill Cornell Medicine Division of Endocrinology Department of Pediatrics University of CaliforniaSan Francisco Department of Nutrition and Food Services University of CaliforniaSan Francisco Department of Epidemiology and Biostatistics University of CaliforniaSan Francisco Department of Biostatistics Mailman School of Public Health Columbia University Department of Biostatistics Columbia University Medical Center

AIM To determine the distribution of anthropometric parameter(AP)-z-scores and characterize associations between medications/serum biomarkers and AP-z-scores in pediatric crohn's disease(cD).METhODS cD patients [chronological age(cA) 21 years] were enrolled in a cross-sectional study. Descriptive statistics were generated for participants' demographic characteristics and key variables of interest. Paired t-tests were used to compare AP-z-scores calculated based on cA(cA z-scores) and bone age(BA)(BA z-scores) for interpretation of AP's. Linear regression was utilized to examine associations between medications and serum biomarkers with AP-z-scores calculated based on cA(n = 82) and BA(n = 49). We reported regression coefficients as well as their corresponding p-values and 95% confidence intervals.RESULTS Mean cA at the time of the study visit was 15.3 ± 3.5(SD; range = 4.8-20.7) years. Mean triceps skinfold(P = 0.039), subscapular skinfold(P = 0.002) and midarm circumference(MAc)(P = 0.001) BA z-scores were higher than corresponding cA z-scores. Medications were positively associated with subscapular skinfold [adalimumab(P = 0.018) and methotrexate(P = 0.027)] and BMI cA z-scores [adalimumab(P = 0.029)]. Azathioprine/6-mercaptopurine were negatively associated with MAc(P = 0.045), subscapular skinfold(P = 0.014), weight(P = 0.002) and BMI(P = 0.013) cA z-scores. ESR, cRP, and WBc count were negatively associated, while albumin and IGF-1 BA z-scores were positively associated, with specific AP z-scores(P height cA z-scores were higher in females, not males, treated with infliximab(P = 0.038). hemoglobin(P = 0.018) was positively associated, while platelets(P = 0.005), ESR(P = 0.003) and cRP(P = 0.039) were negatively associated with height cA z-scores in males, not females. cONcLUSION Our results suggest poor efficacy of thiopurines and a possible sex difference in statural growth response to infliximab in pediatric cD. Prospective longitudinal studies are required.

关键词： Inflammatory bowel disease Azathioprine/6-mercaptopurine Biologics Nutrition

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The use of 5-alpha reductase inhibitors in the treatment of benign prostatic hyperplasia

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Asian Journal of Urology 2018年第1期5卷 28-32页

作者： eric h.Kim John A.Brockman Gerald L.Andriole Division of Urologic Surgery Washington University School of MedicineSt.LouisMOUSA

Benign prostatic hyperplasia(BPh)is characterized by an enlarged prostate,lower urinary tract symptoms(LUTS),and a decreased urinary flow rate.common in older men,BPh is a progressive disease that can eventually lead to complications including acute urinary retention(AUR)and the need for BPh-related surgery.Both normal and abnormal prostate growth is driven by the androgen dihydrotestosterone(DhT),which is formed from testosterone under the influence of 5-alpha reductase.Thus,5-alpha reductase inhibitors(5-ARIs)effectively reduce the serum and intraprostatic concentration of DhT,causing an involution of prostate tissue.Two 5-ARIs are currently available for the treatment of BPhdfinasteride and dutasteride.Both have been demonstrated to decrease prostate volume,improve LUTS and urinary flow rates,which ultimately reduces the risk of AUR and BPh-related surgery.Therefore,either alone or in combination with other BPh medications,5-ARIs are a mainstay of BPh management.

关键词： Benign prostatic hyperplasia 5-alpha reductase inhibitors Lower urinary tract symptoms

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Power hamza Distribution with Application to Lifetime Data

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Journal of Applied Mathematics and Physics 2022年第1期10卷 31-48页

作者： Samuel U. Enogwe chike h. Nwankwo eric U. Oti Department of Statistics Michael Okpara University of Agriculture Umudike Nigeria Department of Statistics Nnamdi Azikiwe University Awka Nigeria Department of Statistics Federal Polytechnic Ekowe Nigeria

In this paper, a three-parameter lifetime distribution named power hamza distribution (Ph) is proposed. The Ph distribution is a useful generalization of the hamza distribution which accommodates heavy-tailed, upside-down bathtub and J-shaped hazard rates making it more flexible than the hamza distribution for modelling various kinds of lifetime data. A comprehensive account of the properties of this distribution is presented. The maximum likelihood estimators of the unknown model parameters are discussed. Finally, a real-life data is analyzed for illustrative purpose proving that the Ph outperforms the hamza distribution and several other lifetime distributions.

关键词： hamza Distribution hazard Rate Function conditional Moments Stochastic Ordering Maximum Likelihood Method

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On strong-scaling and open-source tools for analyzing atom probe tomography data

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npj computational Materials 2021年第1期7卷 148-157页

作者： Markus Kühbach Priyanshu Bajaj huan Zhao Murat hÇelik eric AJägle Baptiste Gault Max-Planck-Institut für Eisenforschung Gmbh(MPIE) DüsseldorfGermany m4p material solutions Gmbh MagdeburgGermany Institute for Advanced Simulation(IAS) Jülich Supercomputing Centre(JSC)JülichGermany Universität der Bundeswehr München NeubibergGermany Department of Materials Imperial College LondonRoyal School of MinesLondonUK

The development of strong-scaling computational tools for high-throughput methods with an open-source code and transparent metadata standards has successfully transformed many computational materials science communities.While such tools are mature already in the condensed-matter physics community,the situation is still very different for many experimentalists.Atom probe tomography(APT)is one example.This microscopy and microanalysis technique has matured into a versatile nano-analytical characterization tool with applications that range from materials science to geology and possibly beyond.here,data science tools are required for extracting chemo-structural spatial correlations from the reconstructed point cloud.For APT and other high-end analysis techniques,post-processing is mostly executed with proprietary software tools,which are opaque in their execution and have often limited performance.Software development by members of the scientific community has improved the situation but compared to the sophistication in the field of computational materials science several gaps remain.This is particularly the case for open-source tools that support scientific computing hardware,tools which enable high-throughput workflows,and open welldocumented metadata standards to align experimental research better with the fair data stewardship principles.To this end,we introduce paraprobe,an open-source tool for scientific computing and high-throughput studying of point cloud data,here exemplified with APT.We show how to quantify uncertainties while applying several computational geometry,spatial statistics,and clustering tasks for post-processing APT datasets as large as two billion ions.These tools work well in concert with Python and hDF5 to enable several orders of magnitude performance gain,automation,and reproducibility.

关键词： hardware Python execution

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Engineering Nannochloropsis oceanica for the production of diterpenoid compounds

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mLife 2023年第4期2卷 428-437页

作者： Zhi-Yan Du Wajid W.Bhat eric Poliner Sean Johnson conor Bertucci Eva Farre Bjoern hamberger Department of Molecular Biosciences and Bioengineering University of Hawaii at ManoaHonoluluHawaiiUSA Department of Biochemistry and Molecular Biology Michigan State UniversityEast LansingMichiganUSA Department of Plant Biology Michigan State UniversityEast LansingMichiganUSA New England Biolabs Inc. 240 County Roadlpswich01938 MAUSA

Photosynthetic microalgae like Nannochloropsis hold enormous potential as sustainable,light-driven biofactories for the production of high-value natural products such as terpenoids.Nannochloropsis oceanica is distinguished as a particularly robust host with extensive genomic and transgenic resources available.Its capacity to grow in wastewater,brackish,and sea waters,coupled with advances in microalgal metabolic engineering,genome editing,and synthetic biology,provides an excellent opportunity.In the present work,we demonstrate how N.oceanica can be engineered to produce the diterpene casbene—an important intermediate in the biosynthesis of pharmacologically relevant macrocyclic diterpenoids.casbene accumulated after stably expressing and targeting the casbene synthase from Daphne genkwa(DgTPS1)to the algal chloroplast.The engineered strains yielded production titers of up to 0.12 mg g^(−1) total dry cell weight(DcW)casbene.heterologous overexpression and chloroplast targeting of two upstream rate-limiting enzymes in the 2-c-methyl-d-erythritol 4-phosphate pathway,coleus forskohlii 1-deoxy-d-xylulose-5-phosphate synthase and geranylgeranyl diphosphate synthase genes,further enhanced the yield of casbene to a titer up to 1.80 mg g^(−1) DcW.The results presented here form a basis for further development and production of complex plant diterpenoids in microalgae.

关键词： casbene microalgae plastid targeting synthetic biology terpene synthase

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In situ mass spectrometry of autoimmune liver diseases

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cellular & Molecular Immunology 2011年第3期8卷 237-242页

作者： christopher L Bowlus Erin h Seeley Joanna Roder Julia Grigorieva heinrich Roder Richard M caprioli M eric Gershwin Division of Gastroenterology and hepatology University of CaliforniaDavisCAUSA Mass Spectrometry Research center Vanderbilt University School of MedicineNashvilleTNUSA Biodesix Steamboat SpringsCOUSA Division of clinical Immunology Allergy and RheumatologyUniversity of CaliforniaDavisCAUSA

Primary biliary cirrhosis(PBc),primary sclerosing cholangitis(PSc)and autoimmune hepatitis(AIh)are the major forms of autoimmune liver diseases each characterized by the destruction of a specific liver cell type and the presence of differing auto-antibodies.We took a proteomic approach utilizing in situ matrix-assisted laser desorption/ionization mass spectrometry(MALDI MS)to obtain profiles directly from liver samples of patients with PBc,PSc,AIh and controls.The ability to precisely localize the region for acquisition of MALDI MS allowed us to obtain profiles from bile ducts,inflammatory infiltrates and hepatocytes from each biopsy sample.Analysis tools developed to identify peaks and compare peaks across diseases and cell types were used to develop models to classify the samples.Using an initial set of testing samples from PBc patients and controls,we identified unique peaks present in bile ducts,inflammatory infiltrates and hepatocytes that could classify samples in a validation cohort with 88–91%accuracy.Interestingly,profiles of PSc and AIh did not differ significantly from PBc.Identification of proteins in these peaks may represent novel autoantigens or effector molecules.These findings illustrate the potential of a proteomic approach to autoimmune diseases with in situ MALDI MS.

关键词： autoimmune hepatitis mass spectrometry primary biliary cirrhosis primary sclerosing cholangitis

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Effects of low-oxygen conditions on embryo growth in the painted turtle,chrysemys picta

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Integrative Zoology 2017年第2期12卷 148-156页

作者： Gerardo A.cORDERO Matthew L.KARNATZ Jon c.SVENDSEN eric J.GANGLOFF Department of Ecology Evolutionand Organismal BiologyIowa State UniversityAmesIowaUSA Technical University of Denmark National Institute of Aquatic ResourcesFreshwater FisheriesSilkeborgDenmark Interdisciplinary centre of Marine and Environmental Research University of PortoPortoPortugal

Low-oxygen conditions(hypoxia;<21%O_(2))are considered unfavorable for growth;yet,embryos of many vertebrate taxa develop successfully in hypoxic subterranean environments.Although enhanced tolerance to hypoxia has be... 详细信息

Low-oxygen conditions(hypoxia;considered unfavorable for growth;yet,embryos of many vertebrate taxa develop successfully in hypoxic subterranean environments.Although enhanced tolerance to hypoxia has been demonstrated in adult reptiles,such as in the painted turtle(chrysemys picta),its effects on sensitive embryo life stages warrant attention.We tested the hypothesis that short-term hypoxia negatively affects growth during day 40 of development in c.picta,when O_(2) demands are highest in embryos.A brief,but severe,hypoxic event(5%O_(2) for 0.5 h)moderately affected embryo growth,causing a 13%reduction in mass(relative to a normoxic control).The same condition had no effect during day 27;instead,a nearly anoxic event(1%O_(2) for 72 h)caused a 5%mass reduction.All embryos survived the egg incubation period.Our study supports the assumption that reptilian embryos are resilient to intermittently low O_(2) in subterranean nests.Further work is needed to ascertain responses to suboptimal O_(2) levels while undergoing dynamic changes in developmental physiology.

关键词： embryo metabolism embryo respiration growth rate nest environment oxygen consumption rate

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Effects of chronic decaffeinated green tea extract supplementation on lipolysis and substrate utilization during upper body exercise

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Journal of Sport and health Science 2021年第2期10卷 237-242页

作者： Sofie Blicher eric Bartholomae Jochen Kressler Department of Exercise and Nutritional Sciences San Diego State UniversitySan DiegoCA 92113USA

Background:Decaffeinated green tea extract(dGTE)can increase fat oxidation during leg exercise,but dGTE is unsuitable for many people(e.g.,those with injuries/disabilities),and its effects on arm exercise and women are unknown.Methods:Eight adults(23-37 years old,4 women)performed an incremental arm cycle test to measure peak oxygen uptake(VO_(2_(peak))),followed by four 1-h trials at 50%VO_(2_(peak).Subjects were randomly assigned to 650 mg of dGTE or placebo(PLA)for 4 weeks followed by a 4-week washout and crossover trial.Blood samples were obtained pre-exercise and post-exercise for glycerol and free fatty acid analysis.Respiratory gases were collected continuously.Results:VO_(2) showed no differences across trials((0.83-0.89)±(0.19-0.25)L/min,p=0.460),neither did energy expenditure((264-266)±(59-77)kcal,p=0.420)nor fat oxidation(dGTE=0.11 to 0.12 g/min vs.PLA=0.10 to 0.09 g/min,p=0.220).Fat oxidation as percentage of energy expenditure was not different for dGTE vs.PLA(23%±12%to 25%±11%vs.23%±10%to 21%±9%,p=0.532).Glycerol concentration increased post-exercise in all trials,independent of treatments(pre=(3.4-5.1)±(0.6-2.6)mg/dL vs.post=(7.9-9.8)±(2.6-3.7)mg/dL,p=0.867,η^(2)=0.005 for interaction),as did free fatty acid((3.5-4.8)±(1.4-2.2)mg/dL vs.(7.2-9.1)±(2.6-4.5)mg/dL,p=0.981,η^(2)=0.000).conclusion:chronic dGTE supplementation had no effect on lipolysis and fat oxidation during arm cycle exercise in men and women.

关键词： Arm exercise cardiometabolic disease Fat oxidation Nutraceutical

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Patterns of antidepressant therapy and clinical outcomes among ischaemic stroke survivors

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Stroke & Vascular Neurology 2021年第3期6卷 384-394,I0018-I0032页

作者： Mark R Etherton Shreyansh Shah Xu haolin Ying Xian Lesley Maisch Deidre hannah Brianna Lindholm Barbara Lytle Laine Thomas eric E Smith Gregg c Fonarow Lee h Schwamm Deepak L Bhatt Adrian F hernandez Emily c O'Brien Neurology Massachusetts General HospitalBostonMassachusettsUSA Neurology Duke University School of MedicineDurhamNorth CarolinaUSA Duke clinical Research Institute Duke UniversityDurhamNorth CarolinaUSA American heart Association Inc DallasTexasUSA clinical Neurosciences University of Calgary Cumming School of MedicineCalgaryAlbertaCanada cardiology Ronald Reagan UCLA Medical CenterLos AngelesCaliforniaUSA cardiovascular Medicine Brigham and Women's HospitalBostonMassachusettsUSA cardiology Duke UniversityDurhamNorth CarolinaUSA Population health Duke Clinical Research InstituteDurhamNorth CarolinaUSA

Background and purpose Depression is common after stroke and is often treated with antidepressant medications(AD).ADs have also been hypothesised to improve stroke recovery,although recent randomised trials were neutral.We investigated the patterns of in-hospital AD initiation after ischaemic stroke and association with clinical and readmission outcomes.Methods All Medicare fee-for-service beneficiaries aged 65 or older hospitalised for ischaemic stroke in participating Get With The Guidelines-Stroke hospitals between April and December 2014 were eligible for this analysis.Outcome measures included days alive and not in a healthcare institution(home time),all-cause mortality and readmission within 1-year postdischarge.Propensity score(PS)-adjusted logistic regression models were used to evaluate the associations between AD use and each outcome measure.We also compared outcomes in patients prescribed selective serotonin reuptake inhibitors(SSRIs)AD versus those prescribed non-SSRI ADs.Results Of 21805 AD naive patients included in this analysis,1835(8.4%)were started on an AD at discharge.Patients started on an AD had higher rates of depression and prior ischaemic stroke,presented with higher admission National Institutes of health Stroke Scale score and were less likely to be discharged home.Similarly,patients started on an SSRI had lower rates of discharge to home.Adjusting for stroke severity,patients started on an AD had worse all-cause mortality,all-cause readmission,major adverse cardiac events,readmission for depression and decreased home-time.however,AD use was also associated with an increased risk for the sepsis,a falsification endpoint,suggesting the presence of residual confounding.conclusions Patients with ischaemic stroke initiated on AD therapy are at increased risk of poor clinical outcomes and readmission even after PS adjustment,suggesting that poststroke depression requiring medication is a poor prognostic sign.Further research is needed to explore the reasons why depression is associated with w

关键词： prescribed admission founding

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