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ImmunoPET imaging of amyloid-beta in a rat model of Alzheimer’s disease with a bispecific,brain-penetrating fusion protein

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Translational Neurodegeneration 2022年第1期11卷 70-83页

作者： gillian bonvicini Stina Syvänen Ken G.Andersson Merja Haaparanta-Solin Francisco López-Picón Dag Sehlin Department of Public Health and Caring Sciences Uppsala University75185 UppsalaSweden BioArctic AB 11251 StockholmSweden Preclinical Imaging Laboratory Turku PET CentreUniversity of Turku20520 TurkuFin-land MediCity Research Laboratory University of Turku20520 TurkuFinland.

Background:Hijacking the transferrin receptor(TfR)is an effective strategy to transport amyloid-beta(Aβ)immuno-positron emission tomography(immunoPET)ligands across the blood-brain barrier(BBB).Such ligands are more sensitive and specific than small-molecule ligands at detecting Aβpathology in mouse models of Alzheimer’s disease(AD).This study aimed to determine if this strategy would be as sensitive in rats and to assess how TfR affinity affects BBB transport of bispecific immunoPET ***:Two affinity variants of the rat TfR antibody,OX26,were chemically conjugated to a F(ab′)2 fragment of the anti-Aβantibody,bapineuzumab(Bapi),to generate two bispecific fusion proteins:OX265-F(ab′)2-Bapi and OX2676-F(ab′)*** analyses were performed 4 h and 70 h post-injection of radioiodinated fusion proteins in wild-type(WT)rats.[124I]I-OX265-F(ab′)2-Bapi was administered to TgF344-AD and WT rats for in vivo PET *** vivo distribution of injected[124I]I-OX265-F(ab′)2-Bapi and Aβpathology were ***:More[125I]I-OX265-F(ab′)2-Bapi was taken up into the brain 4 h post-administration than[124I]I-OX2676-F(ab′)2-Bapi.[124I]I-OX265-F(ab′)2-Bapi PET visualized Aβpathology with significantly higher signals in the TgF344-AD rats than in the WT littermates without Aβ*** PET signals significantly correlated with Aβlevels in AD ***:Affinity to TfR affects how efficiently a TfR-targeting bispecific fusion protein will cross the BBB,such that the higher-affinity bispecific fusion protein crossed the BBB more ***,bispecific immunoPET imaging of brain Aβpathology using TfR-mediated transport provides good imaging contrast between TgF344-AD and WT rats,suggesting that this immunoPET strategy has the potential to be translated to higher species.

关键词： ImmunoPET Transferrin receptor Alzheimer’s disease Amyloid-beta

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Heart failure with preserved ejection fraction

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Journal of Geriatric Cardiology 2013年第4期10卷 369-376页

作者： Marzia Rigollil gillian A Whalley Awhina Health Campus Waitakere Hospital Waitemata District Health Board Private Bag93-503 Auckland New Zealand Division of Cardiology University of Verona Ospedale Maggiore Pie Stefani 1 37126 Verona Italy Faculty of Social and Health Sciences Unitec Institute of Technology Private Bag92025 Auckland NewZealand

Progressive aging of the population and prolonga tion of life expect ancy have led to the ris ng prevalence of heart failure (HF)。Despitethe improvements in medical therapy，the mortality rate of this condition has remained unaccept ably high，becoming t heprimary cause ofdeath in the elderly popul at ion。Almost half of patient swith signs and symptoms of HF are f ound to have a nearly normal ejection fraction，which delineates a distinctclinical syndrome 。known as HF with preserved ejection fraction(HF-PEF) 。While early research focused on the importance of diastolicdys function，more recent studies reported the pathophysological compl exity of the disease with multiple cardiovas 。cular abnormalities contributing to its development and progression。HF-PEF is a challenging maj or health problem with yet no solution as there is no evidence。Based treatment which improves clinical out comes。This review summarizes the state of current knowledge on diagnosis，prognosis and treatment of HF。PEF，with particul ar insights on the pathological characteristics in the elderly population。

关键词： Diastole Echocardiography Heart failure Mortality Preserved ejection fraction

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Mantle plumes: Why the current skepticism?

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Chinese Science Bulletin 2005年第15期50卷 1555-1560页

作者： gillian R. Foulger Department of Earth Sciences Science Laboratories University of Dur-ham South Rd. Durham DH1 3LE U.K.

The present reappraisal of the mantle plume hypothesis is perhaps the most exciting current debate in Earth science. Nevertheless, the fundamental reasons for why it has arisen are often not well understood. They are that 1) many observations do not agree with the predictions of the original model, 2) it is possible that convection of the sort required to generate thermal plumes in the Earth’s mantle does not occur, 3) so many variants of the original model have been invoked to accommodate conflicting data that the plume hypthesis is in practice no longer testable, and 4) al-ternative models are viable, though these have been largely neglected by researchers. Regardless of the final outcome, the present vigorous debate is to be welcomed since it is likely to stimulate new discoveries in a way that unquestioning acceptance of the conventional plume model will not.

关键词：地质学火山热量对流移动覆盖物地球科学

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Being Chinese or Being Different:Chinese Undergraduates’Use of Discourses of Chineseness

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Frontiers of Education in China 2014年第3期9卷 303-326页

作者： gillian SKYRME School of Humanities Massey UniversityPalmerston North 4442New Zealand

Myths about“the Chinese learner”developed from an outsider perspective abound in the Western *** focus of this article,however,is how discourses of Chineseness were used by the Chinese international students themselves who,as undergraduate students in a New Zealand university,were the subjects of my doctoral *** examines the students’notions of Chineseness and how these served in explaining their own narratives,either through identifying with,or distancing themselves from,“Chinese”traits,indicating alternatively a shared experience of the challenges of the new academic culture,or marking themselves out as having a special ability to thrive within *** way they used them,the discourses seemed to serve a purpose of fortifying their sense of identity and *** the end of their study,they were able to reflect carefully on their experiences and discuss new third space identities in which both Chinese and New Zealand values were forging new realities for them.

关键词： Chinese undergraduate Chinese identity negotiation of identity

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Assessment and impact of diastolic function by echocardiography in elderly patients

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Journal of Geriatric Cardiology 2016年第3期13卷 252-260页

作者： Clementina Dugo Marzia Rigolli Andrea Rossi gillian A Whalley Awhina Health Campus Waitemata District Health Board Auckland New Zealand Section of Cardiology Department of Medicine University of Verona Italy Institute of Diagnostic Ultrasound Australasian Sonographers Association Melbourne Australia

Doppler echocardiography is the gold standard for assessment of diastolic dysfunction, which is increasingly recognised as a cause of heart failure, especially in the elderly. Using a combination of Doppler echocardiography techniques, it is possible to identify grades of dia- stolic dysftmction, estimate left ventricular filling pressures and establish the chronicity of diastolic dysfunction. These physiologi- cally-derived measures have been widely validated against invasive measurements of left heart pressures and have been shown to be prog- nostically valuable in a wide range of clinical settings. This review explores the mechanisms, and approaches to the assessment of diastolic dysfunction in the elderly. The challenge for clinicians is to identify pathophysiological changes from those associated with normal ageing. When used in combination, and taking age into account, Doppler echocardiographic parameters are helpful in the assessment of dyspnoea in older patients and provide prognostic insights.

关键词： Diastolic dysfunction Doppler Echocardiography

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Rare case of sclerosing mesenteritis and low grade follicular lymphoma

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World Journal of Clinical Cases 2016年第4期4卷 108-111页

作者： Seema Shah gillian Mahy Enrico Roche the Townsville Hospital

An unusual case of long standing sclerosing mesenteritis;initially presented with recurrent abdominal pain and a mesenteric mass with surrounding fat oedema and stranding with a pseudocapsule and fat ring sign were clearly visualised on the initial computed tomography *** showed diffuse thickening at the root of the mesentery and histology from this specimen revealed fat necrosis and reactive lymphoid tissue consistent with sclerosing *** treatment with steroids and tamoxifen relieved the symptoms and the *** was maintained on *** years later he developed a recurrence of his symptoms and abdominal mass that responded to a course of *** years following this,he developed a follicular Hodgkin’s lymphoma.

关键词： Sclerosing mesenteritis Computerised tomography scan Magnetic resonance imaging scans Tamoxifen Steroids Hodgkin’s lymphoma

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Alice in space

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作者： gillian Beer.

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Segmented sedentary time and physical activity patterns throughout the week from wrist-worn ActiGraph GT3X+ accelerometers among children 7-12 years old

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Journal of Sport and Health Science 2020年第2期9卷 179-188页

作者： gillian McLellan Rosie Arthur Samantha Donnelly Duncan S.Buchan School of Health and Life Sciences The University of the West of ScotlandInstitute of Clinical Exercise and Health ScienceBlantyreG72 OLHScotlandUK

Background:This study examined the volume and patterns of physical activity(PA) and sedentary time(ST) across different segments of the week among boys and ***:A total of 188 children aged 7-12 years wore a wrist-mounted ActiGraph GT3 X+accelerometer for 7 *** spent in PA and ST was calculated using ActiLife *** mean number of minutes of light PA,moderate PA,vigorous PA,moderate-to-vigorous PA(MVPA),and ST were calculated per weekday(before school,during school,and after school) and per weekend day(morning and afternoon-evening).Results:After school represented the greatest accumulation of ST compared with before school and during school *** engaged in225.4 min/day of ST(95% confidence interval(CI):216-235),and girls engaged in 222.2 min/day of ST(95%CI:213-231).During school,boys engaged in significantly more MVPA than girls(46.1 min/day(95%CI:44-48) vs.40.7 min/day(95%CI:39-43)).Across the whole weekday,boys participated in significantly more MVPA than girls(103.9 min/day(95%CI:99-109) vs.95.7 min/day(95%CI:90-101)).The weekend afternoon—evening segment represented the larger accumulation of ST,where boys were significantly more sedentary than girls(367.5 min/day(95%CI:353-382) vs.339.8 min/day(95%CI:325-355),respectively).Conclusion:Our findings suggest that children are highly sedentary and spend little of their time in school in MVPA,especially *** breaks in school elicit increases in light PA and *** work should consider the use of more active breaks within school time to encourage PA and reduce ST.

关键词： Accelerometry School Segments Weekday Youth

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Apoptosis is not an invariable component of in vitro models of cortical cerebral ischaemia

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Cell Research 2004年第3期14卷 241-250页

作者： Paul Alexander JONES,gillian Ruth MAY,Joyce Ann MCLUCKIE,Akinori IWASHITA,John SHARKEY Fujisawa Institute of Neuroscience Division of Neuroscience University of Edinburgh 1 George Square Edinburgh UK Medical Information Eli Lilly and Company Ltd Lilly House Priestley Road Basingstoke RG24 9NL UK Fujisawa Institute of Neurosdence Division of Neuroscience University of Edinburgh 1 George Square Edinburgh UK Medicinal Biology Research Laboratories Fujisawa Pharmaceuticals Co.Ltd. 2-1-6 Kashima Yodogawa-ku Osaka 532-5814 Japan Fujisawa Institute of Neuroscience Division of Neuroscience University of Edinburgh 1 George Square Edinburgh UK

Characterising the mechanisms of cell death following focal cerebral ischaemia has been hampered by a lack of an in vitro assay emulating both the apoptotic and necrotic features observed in vivo. The present study systematically characterised oxygen-glucose-deprivation (OGD) in primary rat cortical neurones to establish a reproducible model with components of both cell-death endpoints. OGD induced a time-dependent reduction in cell viability, with 80% cell death occurring 24 h after 3 h exposure to 0% O2 and 0.5 mM glucose. Indicative of a necrotic component to OGD induced cell death, N-methyl-D-aspartate (NMDA) receptor inhibition with MK-801 attenuated neuronal loss by 60%. The lack of protection by the caspase inhibitors DEVD-CHO and z-VAD-fmk suggested that under these conditions neurones did not die by an apoptotic mechanism. Moderating the severity of the insult by decreasing OGD exposure to 60 min did not reduce the amount of necrosis, but did induce a small degree of apoptosis (a slight reductio

关键词： oxygen-glucose-deprivation caspase cortical necrosis.

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The‘experimental public’in longitudinal health research:views of local leaders and service providers in rural South Africa

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Global Health Research and Policy 2017年第1期2卷 82-93页

作者： Rhian Twine gillian Lewando Hundt Kathleen Kahn MRC/Wits Rural Public Health and Health Transitions Research Unit(Agincourt) School of Public HealthFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa Division of Health Sciences Warwick Medical SchoolUniversity of WarwickCoventryUK INDEPTH Network AccraGhana Epidemiology and Global Health Unit Department of Public Health and Clinical MedicineUmeåUniversityUmeåSweden

Background:The concept of‘experimental public’has been recently applied to publics involved in clinical *** term could also be applied to publics involved in longitudinal research such as health and demographic surveillance *** ethics of practice and public engagement with these experimental publics are of key importance and include issues of informed consent,confidentiality,collection of body tissue samples and fair local ***:Individual(n=11)and focus group(n=5)qualitative semi-structured interviews were conducted with 56 local leaders and service providers regarding their views about research activities in a longitudinal health research study site run by the MRC/Wits Rural Public Health and Health Transitions Research Unit(Agincourt)in rural South *** and inductive thematic analysis was undertaken using NVivo software to identify the emergent ***:There was an understanding of the usefulness of collecting demographic data,but reasons for gathering other contextual data such as on food security,as well as the reasons for collection of blood was less *** appreciation was expressed for feedback of individual results such as blood pressure levels during home-based data collection,there were requests for more results from biomarkers,and for these to be given at home,rather than at the *** were reports of indirect refusals,and offers by leaders to assist in reducing refusal *** were concerns about confidentiality,especially in the publication of *** leaders would have liked to receive more individual level data for planning of services,although they understood this would breach *** providers were concerned about the withdrawal of some services post intervention ***:This experimental public has,over time,developed a nuanced understanding of the reasons for research and the procedures *** concerning fair benefit ranged from requests fo

关键词： Experimental public Longitudinal health research HDSS Rural Ethics of practice

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