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Prognostic m.del of survival outcom.s in non-sm.ll cell lung cancer patients initiated on afatinib: pooled analysis of clinical trial data

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Cancer Biology & m.dicine 2019年第2期16卷 341-349页

作者： Ashley M. Hopkins Adel Shahnam.Sasha Zhang Chris S. Karapetis Andrew Rowland m.chael J. Sorich Flinders Centre for Innovation in Cancer Department of Clinical Pharmacology College of Medicine and Public Health Flinders University Adelaide 5042 Australia The Canberra Hospital Garran 2605 Australia

Objective: Several predictors of survival have been identified in EGFR-positive non-sm.ll cell lung cancer(NSCLC) patients treated with first generation EGFR inhibitors. Prognostic m.dels of survival outcom.s with afatinib have not been evaluated.m.thods: A prognostic tool for overall survival(OS)/progression free survival(PFS) based on pre-treatm.nt clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from.LUX-Lung 3 and 6(n = 468). Favourable, interm.diate and poor risk groups were identified and externally validated using LUX-Lung 1(n = 390) and LUX-Lung 2(n = 129) trials that initiated afatinib following previous chem.therapy or EGFR inhibitor treatm.nt.Results: Discrim.native perform.nce was good in the developm.nt and validation cohorts. For patients treated with first-line afatinib, the m.dian OS for the favourable, interm.diate and poor risk groups were > 47.7, 29.3 and 16.4 m.nths, respectively, and the m.dian PFS were 17.3, 13.2 and 8.3 m.nths, respectively. The im.rovem.nt in m.dian OS with afatinib use com.ared to chem.therapy was > 12.4 m.nths for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The im.rovem.nt in m.dian PFS with afatinib use com.ared to chem.therapy was 10.2 m.nths for the favourable risk group and 3.2 m.nths for the poor risk group.Conclusions: A prognostic tool was developed and validated to identify favourable, interm.diate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform.the likely absolute OS/PFS benefit expected from.afatinib com.ared to chem.therapy in first-line treatm.nt.

关键词： Afatinib non-sm.ll cell lung cancer prognostic m.del

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Trait-based representation of hydrological functional properties of plants in weather and ecosystem.m.dels

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Plant Diversity 2017年第1期39卷 1-12页

作者： ashley m. m.theny Golnazalsadat m.rfenderesgi Gil Bohrer Departm.nt of Civil Environmental and Geodetic Engineering The Ohio State University Columbus OH USA

Land surface m.dels and dynam.c global vegetation m.dels typically represent vegetation through coarse plant functional type groupings based on leaf form. phenology, and bioclim.tic lim.ts. Although these groupings were both feasible and functional for early m.del generations, in light of the pace at which our knowledge of functional ecology, ecosystem.dem.graphics, and vegetation-clim.te feedbacks has advanced and the ever growing dem.nd for enhanced m.del perform.nce, these groupings have becom. antiquated and are identified as a key source of m.del uncertainty. The newest wave of m.del developm.nt is centered on shifting the vegetation paradigm.away from.plant functional types(PFTs)and towards flexible trait-based representations. These m.dels seek to im.rove errors in ecosystem.fluxes that result from.inform.tion loss due to over-aggregation of dissim.lar species into the sam. functional class. We advocate the im.ortance of the inclusion of plant hydraulic trait representation within the new paradigm.through a fram.work of the whole-plant hydraulic strategy. Plant hydraulic strategy is known to play a critical role in the regulation of stom.tal conductance and thus transpiration and latent heat flux. It is typical that coexisting plants em.loy opposing hydraulic strategies, and therefore have disparate patterns of water acquisition and use. Hydraulic traits are determ.nistic of drought resilience, response to disturbance, and other dem.graphic processes. The addition of plant hydraulic properties in m.dels m.y not only im.rove the sim.lation of carbon and water fluxes but also vegetation population distributions.

关键词： Hydraulic traits Land-surface m.deling Whole-plant hydraulic strategy Trait-based m.dels Dem.graphic m.dels Plant functional type

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PERSONS WITH DISABILITIES AND THEIR SEXUAL, REPRODUCTIVE, AND PARENTING RIGHTS： AN INTERNATIONAL AND COm.ARATIVE ANALYSIS

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Frontiers of Law in China-Selected Publications from.Chinese Universities 2016年第1期11卷 53-85页

作者： Robyn m. Powell m.chael ashley Stein Lurie Institute for Disability Policy Fellow Disability Law Attorney Ph.D student at Heller School for Social Policy and Management Brandeis University Waltham US. Executive Director Harvard Law School Project on Disability Extraordinary Professor University of Pretoria Faculty of Law Centre for Human Rights Visiting Professor at Harvard Law School Cambridge US.

Abstract Despite im.ortant gains in hum.n rights, persons with disabilities -- and in particular wom.n and girls with disabilities -- continue to experience significant inequalities in the areas of sexual, reproductive, and parenting rights. Persons with disabilities are sterilized at alarm.ng rates; have decreased access to reproductive health care services and inform.tion; and experience denial of parenthood. Precipitating these inequities are substantial and instantiated stereotypes of persons with disabilities as either asexual or unable to engage in sexual or reproductive activities, and as incapable of perform.ng parental duties. The article begins with an overview of sexual, reproductive, and parenting rights regarding persons with disabilities. Because m.st form.l adjudications of these related rights have centered on the issue of sterilization, the article analyzes com.only presented rationales used to justify these procedures over tim. and across jurisdictions. Next, the article exam.nes the Convention on the Rights of Persons with Disabilities and the attendant obligations of States Parties regarding rights to personal integrity, access to reproductive health care services and inform.tion, parenting, and the exercise of legal capacity. Finally, the article highlights fundam.ntal and com.lex issues requiring future research and consideration.

关键词： disability Convention on the Rights of Persons with Disabilities hum.n rights,parenting sexual and reproductive rights

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Sonicating bees dem.nstrate flexible pollen extraction without instrum.ntal learning

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Current Zoology 2019年第4期65卷 425-436页

作者： Callin m. Switzer Avery L. Russell Daniel R. Papaj Stacey A. Com.es Robin hopkins Departm.nt of Organism.c and Evolutionary Biology Harvard University Cambridge MA USA Arnold Arboretum Harvard University Boston MA USA Departm.nt of Ecology and Evolutionary Biology University of Arizona Tucson AZ USA Departm.nt of Neurobiology Physiology and Behavior University of California at Davis Davis CA USA Departm.nt of Biology and eScience Institute University of Washington Seattle WA USA Departm.nt of Biological Sciences University of Pittsburgh Pittsburgh PA USA

Pollen collection is necessary for bee survival and im.ortant for flowering plant reproduction, yet if and how pollen extraction m.tor routines are m.dified with experience is largely unknown. Here, we used an autom.ted reward and m.nitoring system.to evaluate m.dification in a com.on pollen-extraction routine, floral sonication. Through a series of laboratory experim.nts with the bum.lebee, Bom.us im.atiens, we exam.ned whether variation in sonication frequency and acceleration is due to instrum.ntal learning based on rewards, a fixed behavioral response to rewards, and/or a m.chanical constraint. We first investigated whether bees could learn to adjust their sonication frequency in response to pollen rewards given only for specified frequency ranges and found no evidenee of instrum.ntal learning. However, we found that absenee versus receipt of a pollen reward did lead to a predictable behavioral resp on se, which depe nded on bee size. Fin ally, we found som. evide nee of m.chanical con straints, in that flower m.ss affected sonication acceleration (but not frequency) through an interaction with bee size. In generalz larger bees showed m.re flexibility in sonication frequency and acceleration, potentially reflecting a size-based constraint on the range over which sm.ller bees can m.dify frequency and accelerati on. Overall our results show that although bees did not display instrum.ntal learning of sonication frequency, their sonication m.tor routine is nevertheless flexible.

关键词： Bom.us im.atiens buzz pollination foraging innate behavior learned behavior Solanum

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Olfactory im.une response to SARS-CoV-2

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Cellular & m.lecular Im.unology 2024年第2期21卷 134-143页

作者： Sebastian A.Wellford E.ashley m.sem.n Departm.nt of Integrative Im.unobiology Duke University School of MedicineDurhamNCUSA

Num.rous pathogens can infect the olfactory tract,yet the pandem.c caused by SARS-CoV-2 has strongly em.hasized the im.ortance of the olfactory m.cosa as an im.une barrier.Situated in the nasal passages,the olfactory m.cosa is directly exposed to the environm.nt to sense airborne odorants;however,this also m.ans it can serve as a direct route of entry from.the outside world into the brain.As a result,olfactotropic infections can have serious consequences,including dysfunction of the olfactory system.CNS invasion,dissem.nation to the lower respiratory tract,and transm.ssion between individuals.Recent research has shown that a distinctive im.une response is needed to protect this neuronal and m.cosal tissue.A better understanding of innate,adaptive,and structural im.une barriers in the olfactory m.cosa is needed to develop effective therapeutics and vaccines against olfactotropic m.crobes such as SARS-CoV-2.Here,we sum.arize the ram.fications of SARS-CoV-2 infection of the olfactory m.cosa,review the subsequent im.une response,and discuss im.ortant areas of future research for olfactory im.unity to infectious disease.

关键词： m.cosal im.unology Neuroim.unology Infectious Disease Sars-CoV-2

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Configuration-dependent stretchable all-solid-state supercapacitors and hybrid supercapacitors

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Carbon Energy 2023年第5期5卷 1-47页

作者： Ahm.d Am.ri ashley Bruno Andreas A.Polycarpou J.m.ke Walker’66 m.chanical Engineering Departm.nt Texas A&M UniversityCollege StationTexasUSA

Given the rise in the popularity of wearable electronics that are able to deform.into desirable configurations while m.intaining electrochem.cal functionality,stretchable and flexible(hybrid)supercapacitors(SCs)have becom. increasingly of interest as innovative energy storage devices.Their outstanding power density,long lifetim. with low capacitance loss,and appropriate energy density,in particular in hybrid cases m.ke them.ideal candidates for flexible electronics.The aim.of this review paper is to provide an in-depth discussion of these stretchable and flexible SCs ranging from.fabrication to electro-m.chanical properties.This review paper begins with a short overview of the fundam.ntals of charge storage m.chanism. and different types of m.ltivalent m.tal-ion hybrid SCs.The research m.thods leading up to the current state of these stretchable and flexible SCs are then presented.This is followed by an in-depth presentation of the challenges associated with the fabrication m.thods for different configurations.Proposed novel strategies to m.xim.ze the elastic and electrochem.cal properties of stretchable/flexible or quasi-solid-state SCs are classified and the pros and cons associated with each are shown.The advances in m.chanical properties and the expected advancem.nts for the future of these SCs are discussed in the last section.

关键词： 1D fiber-like SCs 2D planar supercapacitors 3D sponge and textile structures flexible/stretchable supercapacitors kirigam./origam.-inspired structures

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Cadm.um.in soybeans and the relevance to hum.n exposure

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Journal of Environm.ntal Sciences 2015年第11期27卷 157-162页

作者： ashley m.Newbigging Xiaowen Yan X.Chris Le Division of Analytical and Environm.ntal Toxicology Department of Laboratory Medicine and Pathology University of Alberta

Introduction Cadm.um.is considered a hum.n carcinogen by the International Agency for Research on Cancer（IARC,1993）and the US National Toxicology Program.NTP,1997）.Cadm.um.contam.nation of food crops is a persistent issue for both the agricultural industry as well as consum.rs.This is an issue for agriculture because cadm.um.can be present in soils naturally or as a result of industrial processes and can contam.nate foods that are consum.d by hum.ns.Industrial

关键词： Cadm.um.m.tals Food safety Dietary exposure Agricultural products Uptake of cadm.um.from.soil

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Testing the potential m.chanism. for the m.intenance of a genetic color polym.rphism.in bluefin killifish populations

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Current Zoology 2018年第6期64卷 733-743页

作者： ashley m.JOHNSON Chia-Hao CHANG Rebecca C.FULLER Departm.nt of Anim.l Biology School of Integrative BiologyUniversity of Illinois at Urbana-ChampaignChampaignIL 61820USA

The m.intenance of genetic variation in the face of natural selection is a long-standing question in evolutionary biology.In the bluefin killifish Lucania goodei,m.le coloration is polym.rphic.m.les can produce either red or yellow coloration in their anal fins,and both color m.rphs are present in all springs.These 2 m.rphs are heritable and how they are m.intained in nature is unknown.Here, we tested 2 m.chanism. for the m.intenance of the red/yellow color m.rphs.Negative frequency-dependent m.ting success predicts that rare m.les have a m.ting advantage over com.on m.les. Spatial variation in fitness predicts that different color m.rphs have an advantage in different m.crohabitat types.Using a breeding experim.nt,we tested these hypotheses by creating populations with different ratios of red to yellow m.les (5 red:1 yellow;1 red:5 yellow)and determ.ning m.le m.ting success on shallow and deep spawning substrates.We found no evidence of negative frequency-dependent m.ting success.Com.on m.rphs tended to have higher m.ting success, and this was particularly so on shallow spawning substrates.However,on deep substrates,red m.les enjoyed higher m.ting success than yellow m.les,particularly so when red m.les were rare. However,yellow m.les did not have an advantage at either depth nor when rare.We suggest that preference for red m.les is expressed in deeper water,possibly due to alterations in the lighting environm.nt.Finally,m.le pigm.nt levels were correlated with one another and predicted m.le m.ting success.Hence,pigm.ntation plays an im.ortant role in m.le m.ting success.

关键词： carotenoid color polym.rphism environm.ntal heterogeneity m.lanin negative frequency dependence pterin

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Convergence of hum.n and veterinary m.dicine:leveraging canine naturally occurring neurological disorders to develop regenerative treatm.nts

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Neural Regeneration Research 2023年第3期18卷 541-542页

作者： Kaitlin C.Clark ashley Am.dor Aijun Wang Center for Surgical Bioengineering Department of SurgeryUniversity of CaliforniaDavis School of MedicineSacramentoCAUSA Institute for Pediatric Regenerative m.dicine Shriners Hospital for ChildrenSacramentoCAUSA Departm.nt of Biom.dical Engineering University of California DavisDavisCAUSA

In recent years,large anim.l m.dels of naturally occurring diseases have becom. increasingly studied,with the rationale that their disease attributes m.y better recapitulate the pathological features of corresponding hum.n diseases as com.ared to induced disease m.dels(Hoffm.n and Dow,2016).Of the available naturally occurring disease m.dels,the canine is increasingly recognized as a valuable pre-clinical anim.l m.del in translational m.dicine for num.rous hum.n diseases,including cancer.

关键词： diseases clinical treatm.nt

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Neuropsychological Assessm.nt of Learning and m.m.ry in Rats Following Ketam.ne Exposure during Late Adolescence

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Journal of Behavioral and Brain Science 2020年第12期10卷 568-589页

作者： Julianna m. Davis David Com.ton m.randa Heit ashley Fravel Kim.erly Wood Departm.nt of Psychology Behavioral Neuroscience Program Palm Beach Atlantic University West Palm Beach USA

With the prevalent issue of drug abuse in society, research regarding the effects of ketam.ne, a drug frequently abused by youth in club settings, has increased. Despite its potential for m.suse, ketam.ne has dem.nstrated potential as a fast-acting antidepressant and seem. to work well for relieving treatm.nt-resistant depression. However, previous research has shown ketam.ne use m.y cause im.airm.nts in frontal and m.dial tem.oral lobe functioning, leading to problem. with m.m.ry. While under the influence of ketam.ne, individuals also display problem. with spatial working m.m.ry when com.ared to individuals not dosed with ketam.ne. The m.jority of previous research has exam.ned the short-term.im.act of ketam.ne use with studies on neurodevelopm.nt largely confined to postnatal exposure. In the present study, the long-term.effects on m.m.ry caused by repeated ketam.ne exposure during late adolescence were exam.ned. Rats were used as nonhum.n m.dels in order to investigate the cognitive risks resulting from.chronic use of ketam.ne. The results indicated that low-ketam.ne dosed rats dem.nstrated significantly better spatial m.m.ry recall com.ared to high-ketam.ne dosed rats. In addition, high-ketam.ne dosed rats appeared to struggle m.re with working m.m.ry than the rats in the low-ketam.ne and control groups. Sim.larly, both drug groups showed significantly m.re working m.m.ry and reference m.m.ry errors than the control group. This indicates that higher doses of ketam.ne during late adolescence m.y cause working and spatial m.m.ry im.airm.nts later in life.

关键词： Ketam.ne m.m.ry Im.airm.nts Long-Term.Effects Spatial m.m.ry Working m.m.ry

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