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Expanding Treatment Access for Chronic Hepatitis C with Task-shifting in the Era of Direct-acting Antivirals

Journal of Clinical and Translational Hepatology 2017年第2期5卷 130-133页

作者： Eric R.Yoo ryan b.perumpail George Cholankeril Channa R.Jayasekera Aijaz Ahmed Department of Medicine University of Illinois College of Medicine Chicago IL USA Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences Center Memphis TN USA Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Center for Innovation in Global Health Stanford UniversityStanford CA USA

In the United States,the fight to eradicate hepatitis C virus (HCV) infection has been ongoing for many years,but the results have been less than ***,patients with chronic hepatitis C (CHC) were treated with interferon-based regimens,which were associated with frequent adverse effects,suboptimal response rates,and long durations of treatment-of up to 48 *** from specialistphysicians,such as hepatologists and gastroenterologists,was needed to closely follow patients on these medications so as to monitor laboratory values and manage adverse ***,the emergence of direct-acting antiviral (DAA) agents against HCV infection have heralded outstanding progress in terms of safety,tolerability,lack of adverse effects,efficacy,and truncated duration of therapy-12 weeks or less-thereby making the need for close monitoring by specialist-physicians *** the recent approval of DAA agents by the Food and Drug Administration,the treatment model for CHC no longer relies on the limited number of specialist-physicians,which represented a major barrier to treatment access in the past,especially in underserved areas of the United *** propose and share our experiences in adapting a task-shifting treatment model,one that utilizes a relatively larger pool of non-specialist healthcare providers,such as nursing staff (medical assistants,vocational licensed nurses,registered nurses,etc.) and advanced practice providers (nurse practitioners and physician assistants),to perform a variety of important clinical functions in an effort to make DAA-based antiviral therapy widely available against HCV *** recently,task-shifting was implemented by the United States and World Health Organization in the fight against the human immunodeficiency virus and showed encouraging *** on our experiences in implementing this model at our outreach clinics,the majority of HCV-infected patients treated with DAA agents can be easily monitored by

关键词： Task-shifting Treatment Access Underserved Under-resourced Hepatitis C virus HCV Direct acting antivirals DAAs

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Sofosbuvir-based Regimens with Task Shifting Is Cost-effective in Expanding Hepatitis C Treatment Access in the United States

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Journal of Clinical and Translational Hepatology 2017年第1期5卷 16-22页

作者： Channa R.Jayasekera Rachel beckerman Nathaniel Smith ryan b.perumpail Robert J.Wong Zobair M.Younossi Aijaz Ahmed Liver Transplant Program Division of Gastroenterology and HepatologyStanford University Medical CenterStanfordCaliforniaUSA Center for Innovation in Global Health Stanford UniversityStanfordCaliforniaUSA Maple Health Group LLCNew YorkNew YorkUSA Division of Gastroenterology and Hepatology Alameda Health SystemHighland HospitalOaklandCaliforniaUSA Department of Medicine Center for Liver DiseasesInova Fairfax HospitalFalls ChurchVirginiaUSA betty and Guy beatty Center for Integrated Research Inova Health SystemFalls ChurchVirginiaUSA

background and Aims:The current paradigm of specialist physician-managed treatment of chronic hepatitis C virus infection(HCV)is inefficient in absorbing the approximately 3 million patients awaiting treatment in the United *** shifting—whereby specialist physicians screen patients for treatment eligibility but on-treatment monitoring is devolved to more abundant non-physician clinicians—achieves non-inferior treatment outcomes with second generation direct-acting antivirals(2^(nd)Gen DAAs),may increase treatment capacity,and may facilitate greater treatment *** determined the cost effectiveness of 2^(nd)Gen DAAs with respect to interferon-based first-generation DAAs(1^(st)Gen DAAs)within a task-shifted treatment ***:Using a previously described decision-analytic Markov structure,we modeled a hypothetical cohort of 1,000 patients with HCV genotype 1 infection over a lifetime horizon,based upon our outreach clinic's HCV treatment ***-naive and treatment-experienced HCV cohorts were modeled separately,based upon our outr8each clinic's *** response to 2^(nd)Gen DAAs was modeled based on our outreach clinic's *** events,utility,costing,and transition probabilities were sourced from the ***:Driven by improved effectiveness and safety,as well as an expected increase in treatment capacity,2^(nd)Gen DAAs treatment monitored by non-physician clinicians was projected to improve health outcomes and be dominant from a cost-effective perspective versus that of 1^(st)Gen *** were consistent across all assessed patient ***:based on an assumption of increased treatment capacity accompanying a task-shifted treatment model,2^(nd)Gen DAAs-based treatment was cost effective and cost saving as compared to 1^(st)Gen DAAs-based treatment for all HCV patient subgroups assessed.

关键词： Hepatitis C Treatment access Task shifting Cost effectiveness

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Sofosbuvir Use in the Setting of End-stage Renal Disease:A Single Center Experience

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Journal of Clinical and Translational Hepatology 2017年第1期5卷 23-26页

作者： Avin Aggarwal Eric R.Yoo ryan b.perumpail George Cholankeril Radhika Kumari Tami J.Daugherty Alex S.Lapasaran Aijaz Ahmed Division of Gastroenterology and Hepatology Stanford University School of MedicineStanfordCAUSA Department of Medicine University of Illinois College of MedicineChicagoILUSA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences CenterMemphisTNUSA Digestive Health Associates RenoNVUSA

background and Aims:Patients with chronic hepatitis C (CHC) and end-stage renal disease (ESRD) who are dialysisdependent form a unique group,in which safety,tolerability and efficacy of sofosbuvir (SOF)-based direct-acting antivirals (DAAs) need further ***:We performed a retrospective analysis of 14 patients with CHC and ESRD on dialysis who received 15 courses of SOF-based *** evaluated dose escalation to standard-dose SOF in this proof-of-principle ***:Sustained virological response (defined as undetectable viral load at 12 weeks,SVR-12) was achieved in 13 out of the 15 (86.7%) treatment *** (46.6%) patients received reduced half dose as conservative proof-of-principal to mitigate potential *** 13 out of 15 treatment courses,patients completed the designated treatment *** patient was treated twice and developed SVR-12 with the *** patient was lost to follow-up and counted as a *** discontinuations were not due to DAA-related adverse *** were no reports of severe adverse effects or drug ***:We treated CHC patients with ESRD using dose escalation to standard-dose SOF in this proof-of-principle experience and achieved SVR rates comparable to general population.

关键词： Hepatitis C End-stage renal disease Sofosbuvir Direct-acting antivirals

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Rising Rate of Liver Transplantation in the baby boomer Generation with Non-alcoholic Steatohepatitis in the United States

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Journal of Clinical and Translational Hepatology 2017年第3期5卷 193-196页

作者： Osama Siddique Mairin Joseph-Talreja Eric R.Yoo ryan b.perumpail George Cholankeril Stephen A.Harrison Zobair M.Younossi Robert J.Wong Aijaz Ahmed Department of Medicine Memorial Hospital of Rhode Island/Alpert Medical School of Brown University Providence RI USA Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Department of Medicine University of Illinois College of Medicine Chicago IL USA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences Center Memphis TN USA Radcliffe Department of Medicine University of Oxford Oxford United Kingdom Department of Medicine Center for Liver DiseasesInova Fairfax HospitalFalls ChurchVAUSA Division of Gastroenterology and Hepatology Alameda Health SystemHighland HospitalOaklandCAUSA

background and Aims:Nonalcoholic steatohepatitis (NASH) is the most rapidly growing indication for liver transplantation (LT) in the United States and is on a trajectory to become the leading indication for LT in the next *** aimed to study the trends in NASH-related LT among persons born between 1945 and 1965,the baby boomer (bb) ***:We performed a retrospective cohort analysis using population-based data from the United Network for Organ Sharing/Organ Procurement and Transplantation Network registry from 2004-2015 to evaluate the birth cohort-specific trends in liver transplant waitlist registrations and liver transplant surgeries in patients with *** stratified our study population into three birth cohorts:1) birth before 1945,2) birth between 1945 and 1965,and 3) birth after ***:The overall rates of NASH-related waitlist registrations and liver transplant surgeries steadily increased from 2004 to 2015 and were reflective of a sharp rise noted in the NASH bb *** 2004 to 2015,the proportion of bb patients with NASH added to LT waitlist demonstrated an incremental growth,60.6% in 2004 versus 83.2% in 2015 (p by the bb cohort increased from 56.3% in 2004 to 80.0% in 2015 (p bb sub-cohort was mainly responsible for these alarming trends.

关键词： baby boomers Liver transplantation Non-alcoholic steatohepatitis Waitlist

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Underutilization of Living Donor Liver Transplantation in the United States: bias against MELD 20 and Higher

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Journal of Clinical and Translational Hepatology 2016年第3期4卷 169-174页

作者： ryan b.perumpail Eric R.Yoo George Cholankeril Lupe Hogan Melodie Deis Waldo C.Concepcion C.Andrew bonham Zobair M.Younossi Robert J.Wong Aijaz Ahmed Division of Gastroenterology and Hepatology Stanford University School of Medicine Stanford CA USA Department of Medicine University of Illinois College of Medicine Chicago IL USA Division of Gastroenterology and Hepatology University of Tennessee Health Sciences Center Memphis TN USA Division of Surgery Division of Abdominal Transplantation Stanford University School of Medicine Stanford CA USA Department of Medicine Center for Liver Diseases Inova Fairfax HospitalFalls Church VA USA Division of Gastroenterology and Hepatology Alameda Health System Highland Hospital CampusOakland CA USA

background and Aims:Utilization of living donor liver transplantation (LDLT) and its relationship with recipient Model for End-Stage Liver Disease (MELD) needs further evaluation in the United States (U.S.).We evaluated the association between recipient MELD score at the time of surgery and survival following ***:All *** LDLT recipients with MELD< 25 were evaluated using the 1995-2012 United Network for Organ Sharing *** following LDLTwas stratified into three MELD categories (MELD< 15 *** 15-19 *** 20-24) and evaluated using Kaplan-Meier methods and multivariate Cox proportional hazards ***:Overall,2,258 patients underwent *** to patients with MELD< 15,overall 5-year survival following LDLT was similar among patients with MELD 15-19 (80.9% vs.80.3%,p =0.77) and MELD 20-24 (81.2% vs.80.3%,p =0.73).When compared to patients with MELD<15,there was no significant difference in long-term post-LDLT survival among those with MELD 15-19 (HR:1.11,95% CI:0.85-1.45,p =0.45) and a non-significant trend towards lower survival in patients with MELD 20-24 (HR:1.28,95%CI:0.91-1.81,p =0.16).Only 14% of LDLTs were performed in patients with MELD 20-24 and the remaining 86% in patients with MELD< ***:LDLT is underutilized in patients with MELD 20 and higher.

关键词： Living donors Liver transplantation Waitlist Model for End-Stage Liver Disease(MELD)

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Towards global coverage of gridded parameterization for CLImate GENerator(CLIGEN)

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big Earth Data 2024年第1期8卷 142-165页

作者： Andrew T.Fullhart Guillermo E.Ponce-Campos Menberu b.Meles ryan P.McGehee Haiyan Wei Gerardo Armendariz Shea burns David C.Goodrich Southwest Watershed Research Center USDA-ARS TucsonAZUSA School of Natural Resources and the Environment University of ArizonaTucsonAZUSA Sustainable Agricultural Water Systems Unit USDA-ARS DavisCAUSA Agricultural and biosystems Engineering Iowa State UniversityAmesIAUSA

Stochastic weather generators create time series that reproduce key weather dynamics present in long-term *** dataset detailed herein is a large-scale gridded parameterization for CLImate GENerator(CLIGEN)that fills spatial gaps in the coverage of existing regional CLIGEN parameterizations,thereby obtaining near-global availability of combined *** dataset primarily covers countries north of 40°latitude with 0.25°spatial *** CLIGEN parameters were estimated based on 20-year records from four popular global climate *** parameters were statistically downscaled to estimate point-scale values,while point-scale temperature and solar radiation parameters were approximated by direct calculation from high-resolution *** parameter values were used in some cases,such as with wind ***-validation was done to assess the downscaling approach for six precipitation parameters using known point-scale values from ground-based CLIGEN *** parameter values were derived from daily accumulation records at 7,281 stations and high temporal resolution records at 609 *** sensitive parameters,monthly average storm accumulation and maximum 30-minute intensity,were shown have RMSE values of 1.48 mm and 4.67 mm hr^(−1),*** precipitation and the annual number of days with precipitation occurrence were both within 5%of ground-based parameterizations,effectively improving climate data availability.

关键词： Agriculture climate hydrology soil erosion stochastic weather generator

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Machine learning for predicting the outcome of terminal ballistics events

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Defence Technology（防务技术） 2024年第1期31卷 14-26页

作者： Shannon ryan Neeraj Mohan Sushma Arun Kumar AV Julian berk Tahrima Hashem Santu Rana Svetha Venkatesh Applied Artificial Intelligence Institute(A2I2) Deakin University75 Pigdons RdWaurn PondsVIC3216Australia

Machine learning(ML) is well suited for the prediction of high-complexity,high-dimensional problems such as those encountered in terminal *** evaluate the performance of four popular ML-based regression models,extreme gradient boosting(XGboost),artificial neural network(ANN),support vector regression(SVR),and Gaussian process regression(GP),on two common terminal ballistics’ problems:(a)predicting the V50ballistic limit of monolithic metallic armour impacted by small and medium calibre projectiles and fragments,and(b) predicting the depth to which a projectile will penetrate a target of semi-infinite *** achieve this we utilise two datasets,each consisting of approximately 1000samples,collated from public release *** demonstrate that all four model types provide similarly excellent agreement when interpolating within the training data and diverge when extrapolating outside this *** extrapolation is not advisable for ML-based regression models,for applications such as lethality/survivability analysis,such capability is *** circumvent this,we implement expert knowledge and physics-based models via enforced monotonicity,as a Gaussian prior mean,and through a modified loss *** physics-informed models demonstrate improved performance over both classical physics-based models and the basic ML regression models,providing an ability to accurately fit experimental data when it is available and then revert to the physics-based model when *** resulting models demonstrate high levels of predictive accuracy over a very wide range of projectile types,target materials and thicknesses,and impact conditions significantly more diverse than that achievable from any existing analytical *** with numerical analysis tools such as finite element solvers the ML models run orders of magnitude *** provide some general guidelines throughout for the development,application,and reporting of ML models in terminal ballist

关键词： Machine learning Artificial intelligence Physics-informed machine learning Terminal ballistics Armour

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Screen-printed graphite electrode on polyvinyl chloride and parchment strips integrated with genetic programming for in situ nitrate sensing of aquaponic pond water

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Information Processing in Agriculture 2024年第2期11卷 187-201页

作者： Ronnie ConcepcionⅡ bernardo Duarte Maria Gemel Palconit Jonah Jahara baunArgel bandala ryan Rhay Vicerra Elmer Dadios Department of Manufacturing Engineering and Management De La Salle UniversityManila 1004 Philippines MARE-Marine and Environmental Sciences Centre.&ARNET-Aquatic Research Infrastructure Network Associated Laboratory Faculdade de Ciencias da Universidade de LisboaCampo Grande1749-016 LisboaPortugal Departamento de biologia Vegetal da Faculdade de Ciencias da Universidade de Lisboa Campo Grande 1749-016 LisboaPortugal Department of Electronics and Computer Engineering De La Salle UniversityManila 1004 Philppines

Nitrate is the primary water-soluble macronutrient essential for plant growth that is converted from excess fish feeds,fish effluents,and degrading biomaterials on the aquaponic pond floor,and when aquacultural malpractices occur,large amounts of it retain in the water system causing increase rate in eutrophication and toxifies fish and aquaculture *** nitrate sensor prototypes still require performing the additional steps of water sample deionization and dilution and were constructed with expensive *** response to the challenge of sensor enhancement and aquaponic water quality monitoring,this study developed sensitive,repeatable,and reproducible screen-printed graphite electrodes on polyvinyl chloride and parchment paper substrates with silver as electrode material and 60:40 graphite powder:nail polish formulated conductive ink for electrical traces,integrated with 9-gene genetic expression model as a function of peak anodic current and electrochemical test time for nitrate concentration prediction that is embedded into low-power Arduino ESP32 for in situ nitrate sensing in aquaponic pond *** SPE electrical traces were designed on the two types of *** electron microscopy with energy dispersive X-ray confirmed the electrode surface *** cyclic voltammetry using 10 to 100 mg/L KNO3 and water from three-depth regions of the actual pond established the electrochemical test time(10.5 s)and electrode potential(0.135 V)protocol necessary to produce peak current that corresponds to the strength of nitrate ions during *** findings from in situ testing revealed that the proposed sensors have strong linear predictions(R2=0.968 MSE=1.659 for nSPEv and R2=0.966 MSE=4.697 for nSPEp)in the range of 10 to 100 mg/L and best detection limit of 3.15μg/L,which are comparable to other sensors of more complex *** developed three-electrode electrochemical nitrate sensor confirms that it is reliable for bot

关键词： Aquaponic water quality Electrochemical technology Genetic programming Graphite electrode Nitrate sensor Precision agriculture Printed electronics Scanning electron microscopy Screen-printed electrode Voltammetry

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Aging impairs the osteocytic regulation of collagen integrity and bone quality

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bone Research 2024年第1期12卷 78-94页

作者： Charles A.Schurman Serra Kaya Neha Dole Nadja M.Maldonado Luna Natalia Castillo ryan Potter Jacob P.Rose Joanna bons Christina D.King Jordan b.burton birgit Schilling Simon Melov Simon Tang Eric Schaible Tamara Alliston Department of Orthopaedic Surgery University of CaliforniaSan FranciscoCA 94143USA UC berkeley/UCSF Graduate Program in bioengineering San FranciscoCA 94143USA buck Institute for Research on Aging NovatoCA 94945USA Washington University in St Louis Department of OrthopedicsSt.LouisMO 63130USA Advanced Light Source Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA

Poor bone quality is a major factor in skeletal fragility in elderly *** molecular mechanisms that establish and maintain bone quality,independent of bone mass,are unknown but are thought to be primarily determined by *** hypothesize that the age-related decline in bone quality results from the suppression of osteocyte perilacunar/canalicular remodeling(PLR),which maintains bone material *** examined bones from young and aged mice with osteocyte-intrinsic repression of TGFβsignaling(TβRII^(ocy−/−))that suppresses *** control aged bone displayed decreased TGFβsignaling and PLR,but aging did not worsen the existing PLR suppression in male TβRII^(ocy−/−)*** relationship impacted the behavior of collagen material at the nanoscale and tissue scale in macromechanical *** effects of age on bone mass,density,and mineral material behavior were independent of osteocytic TGFβ.We determined that the decline in bone quality with age arises from the loss of osteocyte function and the loss of TGFβ-dependent maintenance of collagen integrity.

关键词： maintain primarily integrity

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Carbon dioxide enrichment affected flower numbers transiently and increased successful post-pollination development stably but without altering final acorn production in mature pedunculate oak (Quercus robur L.)

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Journal of Forestry Research 2024年第4期35卷 1-12页

作者： ryan McClory Richard H.Ellis Martin Lukac Jo Clark Carolina Mayoral Kris M.Hart Andrew R.G.Plackett A.Rob MacKenzie School of Agriculture Policy and DevelopmentUniversity of ReadingAgricultureEarley GateWhiteknights RoadPO Box 237Reading RG66EUUK Faculty of Forestry and Wood Sciences Czech University of Life Sciences PraguePrague 165000Czechia Future Trees Trust Harwell Innovation CentreBuilding 173Curie AvenueHarwellOxford OX110QGUK birmingham Institute of Forest Research University of BirminghamEdgbastonBirmingham B152TTUK School of biosciences University of BirminghamEdgbastonBirmingham B152TTUK School of Geography Earth and Environmental SciencesUniversity of BirminghamEdgbastonBirmingham B152TTUK

Acorn production in oak(Quercus spp.)shows considerable inter-annual variation,known as masting,which provides a natural defence against seed predators but a highly-variable supply of acorns for uses such as in commercial tree planting each *** emissions of greenhouse gases have been very widely reported to influence plant growth and seed or fruit size and quantity via the‘fertilisation effect’that leads to enhanced *** examine if acorn production in mature woodland communities will be affected by further increase in CO_(2),the contents of litter traps from a Free Air Carbon Enrichment(FACE)experiment in deciduous woodland in central England were analysed for numbers of flowers and acorns of pedunculate oak(Quercus robur L.)at different stages of development and their predation levels under ambient and elevated CO_(2) ***-annual variation in acorn numbers was considerable and cyclical between 2015 and 2021,with the greatest numbers of mature acorns in 2015,2017 and 2020 but almost none in *** numbers of flowers,enlarged cups,immature acorns,empty acorn cups,and galls in the litter traps also varied amongst years;comparatively high numbers of enlarged cups were recorded in 2018,suggesting *** at this site is a fruit maturation masting species(i.e.,the extent of abortion of pollinated flowers during acorn development affects mature acorn numbers greatly).Raising the atmospheric CO_(2) concentration by 150μL L^(−1),from early 2017,increased the numbers of immature acorns,and all acorn evidence(empty cups+immature acorns+mature acorns)detected in the litter traps compared to ambient controls by 2021,but did not consistently affect the numbers of flowers,enlarged cups,empty cups,or mature *** number of flowers in the elevated CO_(2) plots’litter traps was greater in 2018 than 2017,one year after CO_(2) enrichment began,whereas numbers declined in ambient *** with CO_(2) also increased the number o

关键词： Quercus robur L. Acorns Masting Pedunculate oak Carbon dioxide

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