47 results on '"Gillespie AL"'
Search Results
2. Burning Follies: The Creation and Failure of the New Zealand Response to Climate Change
- Author
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Gillespie, Al
- Published
- 1997
3. Ocean menace
- Author
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Gillespie, Al
- Published
- 2003
4. Cesspools of shame
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Gillespie, Al
- Published
- 2003
5. The trash tragedy
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Gillespie, Al
- Published
- 2002
6. We Must Invest in Our Future Leaders
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Gillespie, Al
- Subjects
Fire-departments -- Services ,Military leaders -- Services -- Training ,Leadership -- Analysis -- Forecasts and trends ,Market trend/market analysis ,Business, general - Abstract
Byline: Al Gillespie I frequently visit with young leaders from the fire service and the military. Taking the first step into formal leadership can be daunting. When we begin our [...]
- Published
- 2011
7. It's Good to be the Boss
- Author
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Gillespie, Al
- Subjects
Fire-departments -- Recruiting -- Management ,Fire chiefs -- Services ,Career choice -- Analysis ,Recruiting and enlistment -- Analysis ,Industry hiring ,Company business management ,Business, general - Abstract
Byline: Al Gillespie The fire service is a great career choice for those of us who are adrenaline junkies. We enjoy the opportunity to be part of the exciting events [...]
- Published
- 2011
8. Leading When the Seas are at Their Roughest
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Gillespie, Al
- Subjects
Fire-departments -- Human resource management -- Forecasts and trends ,Fire extinction -- Methods ,Fire fighters -- Employment -- Services ,Market trend/market analysis ,Company personnel management ,Business, general - Abstract
Byline: Al Gillespie When my children were growing up, I often threatened to put a brick on top of their heads. The implication was that by putting a weight on [...]
- Published
- 2011
9. XII. Reports on International Organizations and Bodies
- Author
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Matz, Nele, primary, Gillespie, Al, additional, Oemrawsingh, Sangini, additional, Sevenster, Hanna, additional, Wennerås, Pål, additional, Bloch, Felix, additional, Beaulieu, Giovanna M., additional, Opalka, Katia, additional, Ellis, Jaye, additional, Clendon, Ross, additional, Blank, Lutz, additional, Pimenova, Polina, additional, Schrage, Wiek, additional, Zucca, Cristina, additional, Nagai, Masa, additional, Kurukulasuriya, Lal, additional, Mekouar, Mohamed Ali, additional, Vapnek, Jessica, additional, Sucharipa-Behrmann, Lilly, additional, Freestone, David, additional, Salman, Salman A., additional, Di Leva, Charles E., additional, Ragazzi, Maurizio, additional, Bruce, John W., additional, Streck, Charlotte, additional, Scanlon, John, additional, and Palmer, Alice, additional
- Published
- 2002
- Full Text
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10. What public safety needs to understand about the T-Band give-back.
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Gillespie, Al
- Subjects
BROADBAND communication systems ,TELECOMMUNICATION systems ,PUBLIC safety ,CITIES & towns - Abstract
The author discusses the reallocation of the T-Band broadband spectrum to public safety as proposed by the U.S. Congress. He explains that the move will be beneficial to the broadband communications network of the country. The use of the spectrum in large cities is mentioned, noting that a small minority will be affected by the proposal. Some concerns raised regarding possible spectrum deficiency within the public safety community are also addressed.
- Published
- 2012
11. When We Stand Together, Mountains are Climbed.
- Author
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Gillespie, Al
- Subjects
BROADBAND communication systems ,PUBLIC safety ,LEGISLATIVE bills - Abstract
The article discusses the Middle Class Tax Relief and Job Creation Act which includes an provision that authorized the creation of a nationwide broadband network for public safety. The legislation further created FirstNet that will provide governance for the construction, deployment and operation of public-safety broadband network and to be governed by 15-member board of directors. It refers to the legislation as a major accomplishment for public safety achieved through hard work.
- Published
- 2012
12. The Fire Service is a Bargain -- Spread the Word.
- Author
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Gillespie, Al
- Subjects
WATER supply for fire service ,FIRE chiefs ,FIRE prevention ,OVERTIME ,DECISION making - Abstract
The author discusses public misconceptions involving the budget of the fire service. He explains that all expenses incurred by a fire service department are related to business and operations. In order to estimate budget and personnel needs, he asserts that fire chiefs tend to analyze potential response needs and level of risks in a community before making decisions. He also emphasizes the need for fire chiefs to educate the public about the cost of overtime work of firefighters.
- Published
- 2012
13. XII. Reports on International Organizations and Bodies
- Author
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Matz, Nele, Gillespie, Al, Oemrawsingh, Sangini, Sevenster, Hanna, Wennerås, Pål, Bloch, Felix, Beaulieu, Giovanna M., Opalka, Katia, Ellis, Jaye, Clendon, Ross, Blank, Lutz, Pimenova, Polina, Schrage, Wiek, Zucca, Cristina, Nagai, Masa, Kurukulasuriya, Lal, Mekouar, Mohamed Ali, Vapnek, Jessica, Sucharipa-Behrmann, Lilly, Freestone, David, Salman, Salman A., Di Leva, Charles E., Ragazzi, Maurizio, Bruce, John W., Streck, Charlotte, Scanlon, John, and Palmer, Alice
- Published
- 2003
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14. X. Country/Region Reports
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Biniaz, Susan, Maciunas, Silvia, Madrigal Cordero, Patricia, Zapata-Lugo, José Vicente, Ruiz Muller, Manuel, Camargo, Susana, Vives, Sergio, Pagh, Peter, Koivurova, Timo, Fauchald, Ole Kristian, Langlet, David, Mahmoudi, Said, Jóhannsdóttir, Aðalheiður, Szuniewicz, Milena, Loibl, Gerhard, Ruiz, José Juste, Badenes Casino, Margarita, Xaver Perrez, Franz, Peeters, Mairjian, Hertoghs, Marleen, Garabello, Roberta, Vanheusden, Bernard, Deketelaere, Kurt, Sersic, Maja, Wajda, Stanislaw, Turgut, Nükhet, Bogdanovic, Slavko, Begaliyev, Rinat, Jankovic, Petar, Ilic, Zeljka, Ivanova, Jadranka, Vinogradov, Sergei V., Perez, Oren, Rosencranz, Armin, Sripati, Vijayashri, Razzaque, Jona, Kanehara, Atsuko, Bachner, Bryan, Xi, Wang, Lee, Jae-Gon, Glazewski, Jan I., Gillespie, Al, Black, Linley, Hewison, Grant, and Law, Australian Office of International
- Published
- 2003
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15. Make Sure You Have a Safety Net.
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Gillespie, Al
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SERVICE contracts ,FIRE chiefs ,DECISION making ,EMPLOYEE morale ,RESIGNATION from public office - Abstract
The article discusses the merits and demerits of a personal service contract of fire chiefs. It mentions that the contract is valuable as it boosts the employee's morale and makes them more focused at times of difficulty. It further mentions that if the union decides that the fire chief has to leave the office due to a wrong decision of the chief then no contract could prevent him from resigning. It says that fire chiefs should have a contract agreement with the authority.
- Published
- 2012
16. We Reap What We Sow.
- Author
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Gillespie, Al
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BABY boom generation ,FIRE chiefs ,RETIREMENT ,GENERATION X ,FAMILY-work relationship - Abstract
The article focuses on the retirement of baby boomers as fire chiefs in the U.S. It says that the retirement of baby boomers will create job openings for people behind them, in which according to the U.S. Bureau of Labor Statistics, 10 million jobs are available. Furthermore, the Generation X, or people born between 1964 and 1977, and the Generation Y, or people born between 1977 and 1997, sacrifice their personal interests and family for their careers.
- Published
- 2012
17. Effective Leadership Hinges on Solid Partnerships.
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Gillespie, Al
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LEADERSHIP ,FIREFIGHTING ,FIRE fighters ,LEGAL compliance ,INTERPERSONAL relations ,EMERGENCY management - Abstract
The article offers the author's insights on leadership in the fire service. The author notes that a leader has the ability to get the firefighters to perform their functions and put their lives on the line to do them. He cites that compliance and a team which is supportive of each other are needed to improve the organization. He adds that the relationships built with each other makes the team stronger and helps them to easily face the challenges in providing emergency response to the community.
- Published
- 2011
18. The Importance of Truth-Telling When Dealing with Political Leaders.
- Author
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Gillespie, Al
- Subjects
TRUTHFULNESS & falsehood ,FIRE prevention ,FIRE departments ,POLITICIANS ,SOCIAL media - Abstract
The author explains the essence of telling the truth when addressing fire prevention and protection matters to politicians. He believes that fire departments must address the truth for gathering actual data to local authorities and creating suggestions of action for them based on the given data. The author adds that whether in social media or real-life situations, fire departments must be honest with their information in order to make them reliable to both locals and politicians.
- Published
- 2012
19. Why Even Fire Chiefs Need a Personal-Service Contract.
- Author
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Gillespie, Al
- Subjects
FIRE chiefs ,PERSONAL service contracts ,FIRE department personnel ,SERVICE contracts ,CUSTOMER services - Abstract
The article discusses the importance for fire chiefs to have a personal-service contract. The author relates his working relationships with the members of his fire department. He explains that a personal-service contract help a fire chief in an event someone wants to take him out of his position. He adds that when an individual accepts the position of a fire chief, expectations between the individual and the agency having jurisdiction should be articulated in a written document.
- Published
- 2012
20. An online experimental medicine trial on the effect of 28-day simvastatin administration on emotional processing, reward learning, working memory and salivary cortisol in healthy volunteers at risk for depression: OxSTEP protocol.
- Author
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Waters S, De Giorgi R, Quinton AMG, Gillespie AL, Murphy SE, Cowen PJ, and Harmer CJ
- Abstract
Background: Evidence suggests inflammation may be a key mechanism by which psychosocial stress, including loneliness, predisposes to depression. Observational and clinical studies have suggested simvastatin, with its anti-inflammatory properties, may have a potential use in the treatment of depression. Previous experimental medicine trials investigating 7-day use of statins showed conflicting results, with simvastatin displaying a more positive effect on emotional processing compared with atorvastatin. It is possible that statins require longer administration in predisposed individuals before showing the expected positive effects on emotional processing., Aims: Here, we aim to test the neuropsychological effects of 28-day simvastatin administration versus placebo, in healthy volunteers at risk for depression owing to loneliness., Method: This is a remote experimental medicine study. One hundred participants across the UK will be recruited and randomised to either 28-day 20 mg simvastatin or placebo in a double-blind fashion. Before and after administration, participants will complete an online testing session involving tasks of emotional processing and reward learning, processes related to vulnerability to depression. Working memory will also be assessed and waking salivary cortisol samples will be collected. The primary outcome will be accuracy in identifying emotions in a facial expression recognition task, comparing the two groups across time.
- Published
- 2023
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21. Positive and negative personality descriptors: UK dataset of self-referential valence, imageability and subjective frequency ratings of 300 adjectives for use in cognitive-emotional tasks.
- Author
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Raslescu A, Kreicker S, Gillespie AL, Berners-Lee W, Murphy SE, and Harmer CJ
- Abstract
Experimental tasks comparing participants' performance for categorising, remembering, and recognising positive and negative words are widely used in the emotional cognitive domain. Such tasks are commonly used in experimental psychology and psychiatry research, and have been shown to be sensitive biomarkers of depression and antidepressant drug action [1,2]. In addition, several of these tasks investigate self-referential processing i.e., the processing of information relevant to oneself; this has been shown to modify the way emotional words are encoded and remembered and may be a target that is amenable to treatment [3,4]. In practice, the development of such tasks for implementation in research studies often depends on the selection and matching of words according to characteristics such as valence or arousal, imageability, word frequency and word length to investigate differences in a chosen domain of interest whilst keeping important confounds constant. This introduces a need for ratings covering a range of word attributes that have been shown to affect processing. In particular, ratings of self-referential valence (how positively or negatively subjects feel about a word when this is used to describe themselves/their circumstances) have been seldom included in databases, despite the frequent investigation of the concept in research [1,5]. Other important attributes often considered in the process of matching and selection are word imageability and subjective frequency [6,7]. To facilitate the word selection and matching process required in cognitive-emotional task development, the present dataset provides subjective ratings for 150 positive and 150 negative adjectives describing personality characteristics. Across four online surveys, the 300 words were rated on self-referential valence, imageability and subjective frequency by representative samples of 200 UK-based, English-speaking adults. Basic demographics and data on depressive symptoms and state anxiety were collected from all participants. Comprehensive descriptive statistics and word length were calculated for each of the 300 words. All data cleaning and statistical analysis was performed in R. Our work is based on years of experience using the Oxford Emotional Task Battery [1,5] and may be particularly relevant for researchers using self-referential cognitive tasks with UK-based samples., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships which have or could be perceived to have influenced the work reported in this article., (© 2022 Published by Elsevier Inc.)
- Published
- 2022
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22. Pharmacological targeting of cognitive impairment in depression: recent developments and challenges in human clinical research.
- Author
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Colwell MJ, Tagomori H, Chapman S, Gillespie AL, Cowen PJ, Harmer CJ, and Murphy SE
- Subjects
- Humans, Cognition, Synaptic Transmission, Depression drug therapy, Cognitive Dysfunction drug therapy, Cognitive Dysfunction psychology
- Abstract
Impaired cognition is often overlooked in the clinical management of depression, despite its association with poor psychosocial functioning and reduced clinical engagement. There is an outstanding need for new treatments to address this unmet clinical need, highlighted by our consultations with individuals with lived experience of depression. Here we consider the evidence to support different pharmacological approaches for the treatment of impaired cognition in individuals with depression, including treatments that influence primary neurotransmission directly as well as novel targets such as neurosteroid modulation. We also consider potential methodological challenges in establishing a strong evidence base in this area, including the need to disentangle direct effects of treatment on cognition from more generalised symptomatic improvement and the identification of sensitive, reliable and objective measures of cognition., (© 2022. The Author(s).)
- Published
- 2022
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23. Associations Between Statin Use and Negative Affective Bias During COVID-19: An Observational, Longitudinal UK Study Investigating Depression Vulnerability.
- Author
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Gillespie AL, Wigg C, Van Assche I, Murphy SE, and Harmer CJ
- Subjects
- Adult, Antihypertensive Agents, Depression psychology, Humans, Pandemics, COVID-19, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects
- Abstract
Background: There is growing interest in the antidepressant potential of statins. We tested whether statin use is associated with cognitive markers previously found to indicate psychological vulnerability to depression within the context of the COVID-19 pandemic., Methods: Between April 2020 and February 2021, we conducted an observational online study of 2043 adults in the United Kingdom. Participants completed cognitive tasks assessing processes related to depression vulnerability, including affective bias and reward processing. We also measured working memory, medication use, and current psychiatric symptoms. Using mixed analysis of covariance and regression models, we compared participants on statins alone (n = 81), antihypertensive medication alone (n = 126), both medications (n = 111), and on neither medication (n = 1725)., Results: Statin use was associated with reduced recognition of angry and fearful faces (F
1 = 9.19, p = .002; F1 = 6.9, p = .009) and with increased misclassification of these expressions as positive. Increased recognition of angry faces at baseline predicted increased levels of depression and anxiety 10 months later (β = 3.61, p = .027; β = 2.37, p = .002). Statin use was also associated with reduced learning about stimuli associated with loss (F1,1418 = 9.90, p = .002). These indicators of reduced negative bias were not seen in participants taking antihypertensive medication alone, suggesting that they were related to statin use in particular rather than nonspecific demographic factors. In addition, we found no evidence of an association between statin use and impairment in working memory., Conclusions: Statin use was associated with cognitive markers indicative of reduced psychological vulnerability to depression, supporting their potential use as a prophylactic treatment for depression., (Copyright © 2022 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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24. Translating the promise of 5HT 4 receptor agonists for the treatment of depression.
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Murphy SE, de Cates AN, Gillespie AL, Godlewska BR, Scaife JC, Wright LC, Cowen PJ, and Harmer CJ
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- Animals, Mice, Selective Serotonin Reuptake Inhibitors therapeutic use, Antidepressive Agents therapeutic use, Depression drug therapy, Receptors, Serotonin, 5-HT4 metabolism, Serotonin 5-HT4 Receptor Agonists therapeutic use
- Abstract
Animal experimental studies suggest that 5-HT4 receptor activation holds promise as a novel target for the treatment of depression and cognitive impairment. 5-HT4 receptors are post-synaptic receptors that are located in striatal and limbic areas known to be involved in cognition and mood. Consistent with this, 5-HT4 receptor agonists produce rapid antidepressant effects in a number of animal models of depression, and pro-cognitive effects in tasks of learning and memory. These effects are accompanied by molecular changes, such as the increased expression of neuroplasticity-related proteins that are typical of clinically useful antidepressant drugs. Intriguingly, these antidepressant-like effects have a fast onset of their action, raising the possibility that 5-HT4 receptor agonists may be a particularly useful augmentation strategy in the early stages of SSRI treatment. Until recently, the translation of these effects to humans has been challenging. Here, we review the evidence from animal studies that the 5-HT4 receptor is a promising target for the treatment of depression and cognitive disorders, and outline a potential pathway for the efficient and cost-effective translation of these effects into humans and, ultimately, to the clinic.
- Published
- 2021
- Full Text
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25. The Health Promoting Bioactivities of Lactuca sativa can be Enhanced by Genetic Modulation of Plant Secondary Metabolites.
- Author
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Ismail H, Gillespie AL, Calderwood D, Iqbal H, Gallagher C, Chevallier OP, Elliott CT, Pan X, Mirza B, and Green BD
- Abstract
Plant secondary metabolites are protective dietary constituents and rol genes evidently increase the synthesis of these versatile phytochemicals. This study subjected a globally important vegetable, lettuce ( Lactuca sativa ) to a combination of untargeted metabolomics (LC-QTof-MS) and in vitro bioactivity assays. Specifically, we examined the differences between untransformed cultured lettuce (UnT), lettuce transformed with either rolABC (RA) or rolC (RC) and commercially grown (COM) lettuce. Of the 5333 metabolite features aligned, deconvoluted and quantified 3637, 1792 and 3737 significantly differed in RA, RC and COM, respectively, compared with UnT. In all cases the number of downregulated metabolites exceeded the number increased. In vitro bioactivity assays showed that RA and RC (but not COM) significantly improved the ability of L. sativa to inhibit α-glucosidase, inhibit dipeptidyl peptidase-4 (DPP-4) and stimulate GLP-1 secretion. We putatively identified 76 lettuce metabolites (sesquiterpene lactones, non-phenolic and phenolic compounds) some of which were altered by several thousand percent in RA and RC. Ferulic acid levels increased 3033-9777%, aminooxononanoic acid increased 1141-1803% and 2,3,5,4'tetrahydroxystilbene-2-O-β-d-glucoside increased 40,272-48,008%. Compound activities were confirmed using commercially obtained standards. In conclusion, rol gene transformation significantly alters the metabolome of L.sativa and enhances its antidiabetic properties. There is considerable potential to exploit rol genes to modulate secondary metabolite production for the development of novel functional foods. This investigation serves as a new paradigm whereby genetic manipulation, metabolomic analysis and bioactivity techniques can be combined to enable the discovery of novel natural bioactives and determine the functional significance of plant metabolites., Competing Interests: The authors declare no conflict of interest.
- Published
- 2019
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26. Mental health workers perceptions of disaster response in China.
- Author
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Xi Y, Chen R, Gillespie AL, He Y, Jia C, Shi K, Yao Y, Ma X, Liu W, and Chan EYY
- Subjects
- Adult, China, Female, Focus Groups, Health Personnel statistics & numerical data, Humans, Male, Middle Aged, Qualitative Research, Attitude of Health Personnel, Disaster Planning organization & administration, Health Personnel psychology, Mental Health Services
- Abstract
Background: The post-disaster mental health crisis intervention (MHCI) system in China remains immature and unsystematic. We aim to report the perceptions of a large sample of MHCI workers and government administrators and provide recommendations for developing a national mental health disaster response management plan in China., Methods: An in-depth qualitative study was conducted, collecting data from 20 focus-group discussions and 25 key stakeholder interviews. These recruited participants who had been involved in different types of disaster rescue across 7 provinces/cities where disasters have recently occurred. We used thematic analysis to analyze the data and relevant findings were extracted for policy recommendation., Results: Mental health workers' perspectives were examined in detailed according to four core themes: forms of organization, intervention pathway, intervention strategy and technique, and public health information. Post-disaster MHCI should be approached in teams that are integrated with emergency medicine systems, and be led by unified command management. All levels of local health and family planning commission should prepare post-disaster MHCI work plans and build response teams/emergency centres. Future training for MHCI workers should focus on: building a sense of trust within the team; clarifying each member's role; strengthening the screening, assessment and referrals training for psychological professionals; and providing psychological intervention training for Chinese psychiatrists. It is necessary to set up guiding principles for disaster research ethics, mental health rehabilitation and media interaction., Conclusions: Through exploring and analyzing the perceptions of current disaster response mental health workers and government administrators, our findings provide essential recommendations for developing a national to county level post-disaster MHCI emergency management plan and can guide the formulation of relevant laws and regulation in China.
- Published
- 2019
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27. Detailed characterisation of STC-1 cells and the pGIP/Neo sub-clone suggests the incretin hormones are translationally regulated.
- Author
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Gillespie AL, Pan X, Marco-Ramell A, Meharg C, and Green BD
- Subjects
- Cell Line, Cholecystokinin metabolism, Gastrointestinal Hormones metabolism, Humans, Proglucagon metabolism, Gastric Inhibitory Polypeptide metabolism, Glucagon-Like Peptide 1 metabolism, Peptide YY metabolism
- Abstract
STC-1 is a heterogeneous plurihormonal cell line producing several prominent gut peptide hormones. pGIP/Neo is a genetically selected sub-clone of STC-1 with augmented levels of glucose-dependent insulinotropic peptide (GIP). Morphometric parameters, hormone concentrations, mRNA transcripts, hormone immunocytochemistry and nutrient utilisation/production of these two cell lines were compared. Proglucagon-derived peptides (Glucagon-like peptide-1 (GLP-1) and - 2(GLP-2)) were lower in sub-clone cells than progenitor cells. High Content Analysis found altered intracellular GLP-1, GIP, cholecystokinin (CCK) and peptide YY (PYY) levels and differing hormone co-localisation. The proportion pGIP/Neo cells containing GIP immunoreactivity (82%) was greater than STC-1 (65%), as were the proportion with 'GIP only', 'GLP-1+GIP' or 'GIP+PYY' immunoreactivity. Most surprisingly mRNA transcripts of the proglucagon and GIP genes were inversely correlated to the levels of their translated peptides. This strongly suggests that proglucagon and GIP are encoded on 'translationally regulated genes' - a characteristic possessed by other endocrine hormones. Metabolomic profiling revealed differences in cellular nutrient utilisation/production and that under normal culture conditions both cell lines exhibit signs of overflow metabolism. These studies provide an insight into the metabolism and properties of these valuable cells, suggesting for the first time that incretin hormone genes are translationally regulated., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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28. Murine Cytomegalovirus Disrupts Splenic Dendritic Cell Subsets via Type I Interferon-Dependent and -Independent Mechanisms.
- Author
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Nash WT, Gillespie AL, and Brown MG
- Abstract
Dendritic cells (DC) are well-known modulators of immunity. This heterogeneous population is composed of defined subsets that exhibit functional specialization and are critical in initiating responses to pathogens. As such, many infectious agents employ strategies to disrupt DC functioning in attempts to evade the immune system. In some instances, this manifests as an outright loss of these cells. Previous work has suggested that, in the absence of an efficient natural killer (NK) cell response, murine cytomegalovirus (MCMV) induces large amounts of interferon (IFN)-I. This heightened IFN-I response is thought to contribute to conventional DC (cDC) loss and delayed development of T cell immunity. However, the precise role of IFN-I in such cDC loss remains unclear. We investigated the effects of licensed NK cells and IFN-I signaling on splenic cDC subsets during MCMV infection and found that a licensed NK cell response partially protects cDC numbers, but does not prevent increases in serum IFN-I. This suggested that high residual IFN-I could contribute to cDC loss. Therefore, we used multiple strategies to modulate IFN-I signaling during MCMV infection including plasmacytoid DC depletion, IFN-I receptor (IFNAR) blockade, and genetic ablation of IFNAR expression. Interestingly, restriction of IFN-I signals did not substantially preserve either CD8
+ or CD4+ DC total numbers, but resulted in significant retention and/or accumulation of the splenic CD8- CD4- [double negative (DN)] subset. However, the DN DC effect manifested in a DC-extrinsic manner since IFNAR-deficient cells were not preferentially retained over their IFNAR wild-type counterparts in a mixed-chimera setting. Our results show that IFN-I signaling is not responsible for overt cDC toxicity in the setting of acute MCMV infection and emphasize that additional mechanisms contribute to DC loss and require exploration.- Published
- 2017
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29. Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? a systematic review.
- Author
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Gillespie AL, Samanaite R, Mill J, Egerton A, and MacCabe JH
- Subjects
- Clinical Trials as Topic methods, Clozapine therapeutic use, Humans, Prospective Studies, Schizophrenia genetics, Treatment Outcome, Antipsychotic Agents therapeutic use, Schizophrenia diagnosis, Schizophrenia drug therapy
- Abstract
Background: Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes., Method: A systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics)., Results: Nineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons., Conclusions: Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs.
- Published
- 2017
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30. Acute Virus Control Mediated by Licensed NK Cells Sets Primary CD8+ T Cell Dependence on CD27 Costimulation.
- Author
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Teoh JJ, Gamache AE, Gillespie AL, Stadnisky MD, Yagita H, Bullock TN, and Brown MG
- Subjects
- Acute Disease, Animals, CD8-Positive T-Lymphocytes pathology, Cell Differentiation genetics, Cell Differentiation immunology, Herpesviridae Infections genetics, Herpesviridae Infections pathology, Killer Cells, Natural pathology, Mice, Mice, Knockout, Signal Transduction genetics, CD8-Positive T-Lymphocytes immunology, Herpesviridae Infections immunology, Killer Cells, Natural immunology, Muromegalovirus immunology, Signal Transduction immunology, Tumor Necrosis Factor Receptor Superfamily, Member 7 immunology
- Abstract
NK cells represent a critical first-line of immune defense against a bevy of viral pathogens, and infection can provoke them to mediate supportive and suppressive effects on virus-specific adaptive immunity. In mice expressing MHC class I D
k (Dk ), a major murine CMV (MCMV) resistance factor and self-ligand of the inhibitory Ly49G2 (G2) receptor, licensed G2+ NK cells provide essential host resistance against MCMV infection. Additionally G2+ NK cell responses to MCMV increase the rate and extent of dendritic cell (DC) recovery, as well as early priming of CD8+ T cell effectors in response to MCMV. However, relatively little is known about the NK cell effect on costimulatory ligand patterns displayed by DCs or on ensuing effector and memory T cell responses. In this study, we found that CD27-dependent CD8+ T cell priming and differentiation are shaped by the efficiency of NK responses to virus infection. Surprisingly, differences in specific NK responses to MCMV in Dk -disparate mice failed to distinguish early DC costimulatory patterns. Nonetheless, although CD27 deficiency did not impede licensed NK-mediated resistance, CD70 and CD27 were required to efficiently prime and regulate effector CD8+ T cell differentiation in response to MCMV, which eventually resulted in biased memory T cell precursor formation in Dk mice. In contrast, CD8+ T cells accrued more slowly in non-Dk mice and eventually differentiated into terminal effector cells regardless of CD27 stimulation. Disparity in this requirement for CD27 signaling indicates that specific virus control mediated by NK cells can shape DC costimulatory signals needed to prime CD8+ T cells and eventual T cell fate decisions., Competing Interests: Disclosure The authors declare no conflict of interest., (Copyright © 2016 by The American Association of Immunologists, Inc.)- Published
- 2016
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31. The bioactive effects of casein proteins on enteroendocrine cell health, proliferation and incretin hormone secretion.
- Author
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Gillespie AL and Green BD
- Subjects
- Caseins metabolism, Cell Line, Chymotrypsin metabolism, Diabetes Mellitus metabolism, Enteroendocrine Cells cytology, Enteroendocrine Cells metabolism, Glucagon-Like Peptide 1 analysis, Hydrolysis, Caseins pharmacology, Cell Proliferation drug effects, Enteroendocrine Cells drug effects, Glucagon-Like Peptide 1 metabolism
- Abstract
Previous studies suggest that casein exerts various anti-diabetic effects. However, it is not known which casein proteins are bioactive, nor their effects on enteroendocrine cells. This study evaluated the effects of intact whole casein, intact individual proteins (alpha, beta and kappa casein) and hydrolysates on an enteroendocrine cell line. High content analysis accurately monitored changes in cell health and intracellular glucagon-like peptide-1 (GLP-1) content. Cheese ripening duration and GLP-1 secretory responses were also considered. Beta casein significantly stimulated enteroendocrine cell proliferation and all caseins were potent GLP-1 secretagogues (except kappa casein). Interestingly the GLP-1 secretory activity was almost always lost or significantly reduced upon hydrolysis with proteolytic enzymes. Only pepsin-derived beta casein hydrolysates had significantly increased potency compared with the intact protein, but this was diminished with prolonged hydrolysis. In conclusion casein proteins are not detrimental to enteroendocrine cells, and alpha and beta casein are particularly beneficial stimulating proliferation and GLP-1 secretion., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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32. Genomic Modifiers of Natural Killer Cells, Immune Responsiveness and Lymphoid Tissue Remodeling Together Increase Host Resistance to Viral Infection.
- Author
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Gillespie AL, Teoh J, Lee H, Prince J, Stadnisky MD, Anderson M, Nash W, Rival C, Wei H, Gamache A, Farber CR, Tung K, and Brown MG
- Subjects
- Animals, Chromosome Mapping, Cytomegalovirus Infections pathology, Female, Genes, MHC Class I immunology, Genetic Loci, Genotype, Histocompatibility Antigens Class I genetics, Histocompatibility Antigens Class I metabolism, Humans, Immunity, Cellular, Lymphoid Tissue immunology, Male, Mice, Mice, Inbred C57BL, Polymorphism, Genetic, Receptors, Immunologic metabolism, Spleen immunology, Spleen pathology, Cytomegalovirus Infections immunology, Genes, MHC Class I genetics, Killer Cells, Natural immunology, Muromegalovirus immunology, Quantitative Trait Loci genetics, Receptors, Immunologic genetics
- Abstract
The MHC class I D(k) molecule supplies vital host resistance during murine cytomegalovirus (MCMV) infection. Natural killer (NK) cells expressing the Ly49G2 inhibitory receptor, which specifically binds D(k), are required to control viral spread. The extent of D(k)-dependent host resistance, however, differs significantly amongst related strains of mice, C57L and MA/My. As a result, we predicted that relatively small-effect modifier genetic loci might together shape immune cell features, NK cell reactivity, and the host immune response to MCMV. A robust D(k)-dependent genetic effect, however, has so far hindered attempts to identify additional host resistance factors. Thus, we applied genomic mapping strategies and multicolor flow cytometric analysis of immune cells in naive and virus-infected hosts to identify genetic modifiers of the host immune response to MCMV. We discovered and validated many quantitative trait loci (QTL); these were mapped to at least 19 positions on 16 chromosomes. Intriguingly, one newly discovered non-MHC locus (Cmv5) controlled splenic NK cell accrual, secondary lymphoid organ structure, and lymphoid follicle development during MCMV infection. We infer that Cmv5 aids host resistance to MCMV infection by expanding NK cells needed to preserve and protect essential tissue structural elements, to enhance lymphoid remodeling and to increase viral clearance in spleen.
- Published
- 2016
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33. Whey proteins have beneficial effects on intestinal enteroendocrine cells stimulating cell growth and increasing the production and secretion of incretin hormones.
- Author
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Gillespie AL, Calderwood D, Hobson L, and Green BD
- Subjects
- Animals, Cell Line, Cell Proliferation drug effects, Cell Survival drug effects, Enteroendocrine Cells metabolism, Glucagon-Like Peptide 1 metabolism, Hypoglycemic Agents pharmacology, Intestinal Mucosa metabolism, Intestines cytology, Lactalbumin analysis, Lactoglobulins analysis, Lactoglobulins pharmacology, Mice, Protein Hydrolysates pharmacology, Enteroendocrine Cells drug effects, Incretins metabolism, Intestines drug effects, Whey Proteins pharmacology
- Abstract
Whey protein has been indicated to curb diet-induced obesity, glucose intolerance and delay the onset of type 2 diabetes mellitus. Here the effects of intact crude whey, intact individual whey proteins and beta-lactoglobulin hydrolysates on an enteroendocrine (EE) cell model were examined. STC-1 pGIP/neo cells were incubated with several concentrations of yogurt whey (YW), cheese whey (CW), beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and bovine serum albumin (BSA). The findings demonstrate that BLG stimulates EE cell proliferation, and also GLP-1 secretion (an effect which is lost following hydrolysis with chymotrypsin or trypsin). ALA is a highly potent GLP-1 secretagogue which also increases the intracellular levels of GLP-1. Conversely, whey proteins and hydrolysates had little impact on GIP secretion. This appears to be the first investigation of the effects of the three major proteins of YW and CW on EE cells. The anti-diabetic potential of whey proteins should be further investigated., (Copyright © 2015 Elsevier Ltd. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
34. Lipid biomarkers in ooids from different locations and ages: evidence for a common bacterial flora.
- Author
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Summons RE, Bird LR, Gillespie AL, Pruss SB, Roberts M, and Sessions AL
- Subjects
- Bacteria classification, Gas Chromatography-Mass Spectrometry, Radiometric Dating, Bacteria metabolism, Fatty Acids metabolism, Geologic Sediments microbiology, Hydrocarbons metabolism, Terpenes metabolism
- Abstract
Ooids are one of the common constituents of ancient carbonate rocks, yet the role that microbial communities may or may not play in their formation remains unresolved. To search for evidence of microbial activity in modern and Holocene ooids, samples collected from intertidal waters, beaches and outcrops in the Bahamas and in Shark Bay in Western Australia were examined for their contents of lipid biomarkers. Modern samples from Cat and Andros islands in the Bahamas and from Carbla Beach in Hamelin Pool, Western Australia, showed abundant and notably similar distributions of hydrocarbons, fatty acids (FAs) and alcohols. A large fraction of these lipids were bound into the carbonate matrix and only released on acid dissolution, which suggests that these lipids were being incorporated continuously during ooid growth. The distributions of hydrocarbons, and their disparate carbon isotopic signatures, were consistent with mixed input from cyanobacteria together with small and variable amounts of vascular plant leaf wax [C27 -C35 ; δ(13) C -25 to -32‰Vienna Pee Dee Belemnite (VPDB)]. The FAs comprised a complex mixture of C12 -C18 normal and branched short-chain compounds with the predominant straight-chain components attributable to bacteria and/or cyanobacteria. Branched FA, especially 10-MeC16 and 10-MeC17 , together with the prevalence of elemental sulfur in the extracts, indicate an origin from sulfate-reducing bacteria. The iso- and anteiso-FA were quite variable in their (13) C contents suggesting that they come from organisms with diverse physiologies. Hydrogen isotopic compositions provide further insight into this issue. FAs in each sample show disparate δD values consistent with inputs from autotrophs and heterotrophs. The most enigmatic lipid assemblage is an homologous series of long-chain (C24 -C32 ) FA with pronounced even carbon number preference. Typically, such long-chain FA are thought to come from land plant leaf wax, but in this case, their (13) C-enriched isotopic signatures compared to co-occurring n-alkanes (e.g., Hamelin Pool TLE FA C24 -C32 ; δ(13) C -20 to -24.2‰ VPDB; TLE n-alkanes δ(13) C -24.1 to -26.2 -‰VPDB) indicate a microbial origin, possibly sulfate-reducing bacteria. Lastly, we identified homohopanoic acid and bishomohopanol as the primary degradation products of bacterial hopanoids. The distributions of lipids isolated from Holocene oolites from the Rice Bay Formation of Cat Island, Bahamas were very similar to the beach ooids described above and, in total, these modern and fossil biomarker data lead us to hypothesize that ooids are colonized by a defined microbial community and that these microbes possibly mediate calcification., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
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35. Molecular indicators of microbial diversity in oolitic sands of Highborne Cay, Bahamas.
- Author
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Edgcomb VP, Bernhard JM, Beaudoin D, Pruss S, Welander PV, Schubotz F, Mehay S, Gillespie AL, and Summons RE
- Subjects
- Bacteria genetics, Bahamas, Base Sequence, Biomarkers analysis, Calcium Carbonate analysis, Chromatography, High Pressure Liquid, Lipids analysis, Molecular Sequence Data, RNA, Ribosomal, 16S genetics, Sequence Analysis, DNA, Bacteria chemistry, Biodiversity, Biota, Geologic Sediments analysis, Silicon Dioxide
- Abstract
Microbialites (stromatolites and thrombolites) are mineralized mat structures formed via the complex interactions of diverse microbial-mat communities. At Highborne Cay, in the Bahamas, the carbonate component of these features is mostly comprised of ooids. These are small, spherical to ellipsoidal grains characterized by concentric layers of calcium carbonate and organic matter and these sand-sized particles are incorporated with the aid of extra-cellular polymeric substances (EPS), into the matrix of laminated stromatolites and clotted thrombolite mats. Here, we present a comparison of the bacterial diversity within oolitic sand samples and bacterial diversity previously reported in thrombolitic and stromatolitic mats of Highborne Cay based on analysis of clone libraries of small subunit ribosomal RNA gene fragments and lipid biomarkers. The 16S-rRNA data indicate that the overall bacterial diversity within ooids is comparable to that found within thrombolites and stromatolites of Highborne Cay, and this significant overlap in taxonomic groups suggests that ooid sands may be a source for much of the bacterial diversity found in the local microbialites. Cyanobacteria were the most diverse taxonomic group detected, followed by Alphaproteobacteria, Gammaproteobacteria, Planctomyces, Deltaproteobacteria, and several other groups also found in mat structures. The distributions of intact polar lipids, the fatty acids derived from them, and bacteriohopanepolyols provide broad general support for the bacterial diversity identified through analysis of nucleic acid clone libraries., (© 2013 Blackwell Publishing Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
36. Large D/H variations in bacterial lipids reflect central metabolic pathways.
- Author
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Zhang X, Gillespie AL, and Sessions AL
- Subjects
- Deuterium analysis, Fatty Acids biosynthesis, Hydrogen analysis, NADP metabolism, Proteobacteria growth & development, Deuterium metabolism, Hydrogen metabolism, Lipids biosynthesis, Proteobacteria metabolism
- Abstract
Large hydrogen-isotopic (D/H) fractionations between lipids and growth water have been observed in most organisms studied to date. These fractionations are generally attributed to isotope effects in the biosynthesis of lipids, and are frequently assumed to be approximately constant for the purpose of reconstructing climatic variables. Here, we report D/H fractionations between lipids and water in 4 cultured members of the phylum Proteobacteria, and show that they can vary by up to 500 per thousand in a single organism. The variation cannot be attributed to lipid biosynthesis as there is no significant change in these pathways between cultures, nor can it be attributed to changing substrate D/H ratios. More importantly, lipid/water D/H fractionations vary systematically with metabolism: chemoautotrophic growth (approximately -200 to -400 per thousand), photoautotrophic growth (-150 to -250 per thousand), heterotrophic growth on sugars (0 to -150 per thousand), and heterotrophic growth on TCA-cycle precursors and intermediates (-50 to +200 per thousand) all yield different fractionations. We hypothesize that the D/H ratios of lipids are controlled largely by those of NADPH used for biosynthesis, rather than by isotope effects within the lipid biosynthetic pathway itself. Our results suggest that different central metabolic pathways yield NADPH--and indirectly lipids--with characteristic isotopic compositions. If so, lipid deltaD values could become an important biogeochemical tool for linking lipids to energy metabolism, and would yield information that is highly complementary to that provided by (13)C about pathways of carbon fixation.
- Published
- 2009
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- View/download PDF
37. Gastric Digestion of Proteids.
- Author
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Gillespie AL
- Published
- 1893
38. The Physiology of the Salmon in Fresh Water.
- Author
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Boyd FD, Dunlop JC, Gillespie AL, Gulland GL, Greig ED, Mahalanobis SC, Newbigin MI, and Paton DN
- Published
- 1898
- Full Text
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39. On the Weather, Influenza, and Disease from the Infirmary Records.
- Author
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Gillespie AL
- Published
- 1896
40. Some Deductions from a Study of the Development of the Heart.
- Author
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Gibson GA and Gillespie AL
- Published
- 1892
41. Notes on Toxic Effects of Exalgin.
- Author
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Gillespie AL
- Published
- 1892
42. Notes on a Case of Paroxysmal Methæmoglobinuria.
- Author
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Gillespie AL
- Published
- 1892
43. The Action of Acids and Alkalies, and of Some Other Drugs, on the Secretions of the Body.
- Author
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Gillespie AL
- Published
- 1894
44. Statistics Concerning the Patients Admitted with Alcoholic Symptoms to the Royal Infirmary, Edinburgh, for the Five Years from 1st October 1889 to 20th September 1894.
- Author
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Gillespie AL
- Published
- 1895
45. Note on the Presence of Different Albumoses in the Amniotic Fluid.
- Author
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Gillespie AL
- Published
- 1894
46. Some Practical Results from the Chemical Examination of the Contents of the Healthy Stomach.
- Author
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Gillespie AL
- Published
- 1893
47. Report of the Royal Maternity and Simpson Memorial Hospital for the Quarter Ending 31st July 1890.
- Author
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Turner D and Gillespie AL
- Published
- 1891
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