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Search Results: 1 - 10 of 152534 matches for " Rebecca H. Chisholm "
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Building a Morphogen Gradient without Diffusion in a Growing Tissue
Rebecca H. Chisholm,Barry D. Hughes,Kerry A. Landman
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0012857
Abstract: In many developmental systems, spatial pattern arises from morphogen gradients, which provide positional information for cells to determine their fate. Typically, diffusion is thought to be the mechanism responsible for building a morphogen gradient. An alternative mechanism is investigated here. Using mathematical modeling, we demonstrate how a non-diffusive morphogen concentration gradient can develop in axially growing tissue systems, where growth is due to cell proliferation only. Two distinct cases are considered: in the first, all cell proliferation occurs in a localized zone where active transcription of a morphogen-producing gene occurs, and in the second, cell proliferation is uniformly distributed throughout the tissue, occurring in both the active transcription zone and beyond. A cell containing morphogen mRNA produces the morphogen protein, hence any gradient in mRNA transcripts translates into a corresponding morphogen protein gradient. Proliferation-driven growth gives rise to both advection (the transport term) and dilution (a reaction term). These two key mechanisms determine the resultant mRNA transcript distribution. Using the full range of uniform initial conditions, we show that advection and dilution due to cell proliferation are, in general, sufficient for morphogen gradient formation for both types of axially growing systems. In particular, mRNA transcript degradation is not necessary for gradient formation; it is only necessary with localized proliferation for one special value of the initial concentration. Furthermore, the morphogen concentration decreases with distance away from the transcription zone, except in the case of localized proliferation with the initial concentration sufficiently large, when the concentration can either increase with distance from the transcription zone or sustain a local minimum. In both localized and uniformly distributed proliferation, in order for a concentration gradient to form across the whole domain, transcription must occur in a zone equal to the initial domain size; otherwise, it will only form across part of the tissue.
Growth patterns in Onychophora (velvet worms): lack of a localised posterior proliferation zone
Georg Mayer, Chiharu Kato, Bj?rn Quast, Rebecca H Chisholm, Kerry A Landman, Leonie M Quinn
BMC Evolutionary Biology , 2010, DOI: 10.1186/1471-2148-10-339
Abstract: Using in vivo incorporation of the DNA replication marker BrdU (5-bromo-2'-deoxyuridine) and anti-phospho-histone H3 immunolabelling, we found that a localised posterior region of proliferating cells does not occur at any developmental stage in onychophoran embryos. This contrasts with a localised pattern of cell divisions at the posterior end of annelid embryos, which we used as a positive control. Based on our data, we present a mathematical model, which challenges the paradigm that a localised posterior proliferation zone is necessary for segment patterning in short germ developing arthropods.Our findings suggest that a posterior proliferation zone was absent in the last common ancestor of Onychophora and Arthropoda. By comparing our data from Onychophora with those from annelids, arthropods, and chordates, we suggest that the occurrence of a "posterior growth zone" currently cannot be used to support the homology of segmentation between these three animal groups.The most obvious subdivision of the body into serially repeated units or segments occurs in annelids (ringed worms), panarthropods (onychophorans, tardigrades and arthropods), and chordates (including vertebrates, urochordates and cephalochordates). During embryonic development, segments are commonly believed to originate from the so-called "posterior growth zone" (review [1]). However, this term has been applied very broadly in the past, which has resulted in ambiguity. For example, the occurrence of a "posterior growth zone" has been used to support the homology of segmentation either specifically in annelids and panarthropods [2-4] or in all three groups of segmented animals, suggesting that segmentation was present in their last common ancestor [1,5-8].Traditionally, the term "posterior growth zone" has been used to describe a localised and highly proliferative terminal body region, which has been dubbed the "proliferating area" or "zone of proliferation" [9-11]. While it seems clear that such a loca
Oral Histories of a Layered Landscape: The Rushworth Oral History Project
Keir Reeves,E. Rebecca Sanders,Gordon Chisholm
Public History Review , 2007,
Abstract: This article reflects the authors’ experience of undertaking an oral history project in the regional Victorian town of Rushworth. The authors of the article contend that to conduct an investigation of the natural and cultural heritage of the town and surrounding forests is also to engage in an archaeology of historical landscapes. The authors, after articulating the theoretical and methodological issues of oral history, name and trace the various historical layers of the landscape of Rushworth and the forest that surrounds the town. They argue that the use of oral history in conjunction with cultural landscape analysis enables a deeper understanding of the cultural complexity of the history of Rushworth and the surrounding region. Broader issues concerning regional identity and the role of historians in providing a greater understanding of the community in the present day are also evaluated.
Progresso e mimesis: ideias políticas, imita??o e desenvolvimento
Chisholm, Robert;
Lua Nova: Revista de Cultura e Política , 2009, DOI: 10.1590/S0102-64452009000200004
Abstract: comparative political science has ignored the central role that political ideas and models have on the creation and development of institutions. with the collapse of the soviet bloc and the intellectual fervor that accompanied this event, possibilities of paying attention to the effects of political thought grew. articulated by political thinkers, ideas direct actions, reflect dominant understandings among elites on the truth or provide a basis for criticism of these understandings. in this sense, their study may reveal some aspects of the effort to set up a regime. this article suggests an approach to the problem: focusing on how ideas are adopted, adapted and supported by the political actors.
Exploring UK attitudes towards unlicensed medicines use: a questionnaire-based study of members of the general public and physicians
Chisholm A
International Journal of General Medicine , 2012, DOI: http://dx.doi.org/10.2147/IJGM.S28341
Abstract: ring UK attitudes towards unlicensed medicines use: a questionnaire-based study of members of the general public and physicians Original Research (1870) Total Article Views Authors: Chisholm A Published Date January 2012 Volume 2012:5 Pages 27 - 40 DOI: http://dx.doi.org/10.2147/IJGM.S28341 Received: 17 November 2011 Accepted: 06 December 2011 Published: 10 January 2012 Alison Chisholm Omega Scientific, Yately, UK Aims: To undertake a questionnaire-based study to evaluate attitudes towards the use of unlicensed medicines among prescribing doctors and members of the general public (ie, patients). The study also aimed to explore the factors that influence physicians' prescribing decisions and priorities, and to understand the knowledge of the medicines licensing system among members of the public. Methods: Novartis Pharmaceuticals UK Ltd funded the online interview of 500 members of the general public and 249 prescribing physicians. Best practice standards were followed for questionnaire-based studies; no specific treatments or conditions were mentioned or discussed. Results: Few of the participating physicians, only 14%, were very familiar with the UK General Medical Council (GMC) guidelines on the use of unlicensed medicines and just 17% felt very comfortable prescribing an unlicensed medication when a licensed alternative was available. Key physician concerns included the lack of safety data (76%), legal implications (76%), and safety monitoring associated with unlicensed medicine use (71%). Patients and physicians agreed that safety and efficacy are the most important prescribing considerations, although 48% of participating physicians were worried that budget pressures may increase pressure to prescribe unlicensed medications on the basis of cost. A high proportion of patients (81%) also indicated some degree of concern, were they to be prescribed an unlicensed medication when a licensed alternative was available specifically because it costs less. Conclusions: This UK-based questionnaire study suggests pervasive concerns among prescribers over the safety, monitoring, and legal implications of unlicensed prescribing. High levels of concern were expressed among patients and physicians if cost were to become an influential factor when making decisions between licensed and unlicensed medications.
Exploring UK attitudes towards unlicensed medicines use: a questionnaire-based study of members of the general public and physicians
Chisholm A
International Journal of General Medicine , 2012,
Abstract: Alison ChisholmOmega Scientific, Yately, UKAims: To undertake a questionnaire-based study to evaluate attitudes towards the use of unlicensed medicines among prescribing doctors and members of the general public (ie, patients). The study also aimed to explore the factors that influence physicians' prescribing decisions and priorities, and to understand the knowledge of the medicines licensing system among members of the public.Methods: Novartis Pharmaceuticals UK Ltd funded the online interview of 500 members of the general public and 249 prescribing physicians. Best practice standards were followed for questionnaire-based studies; no specific treatments or conditions were mentioned or discussed.Results: Few of the participating physicians, only 14%, were very familiar with the UK General Medical Council (GMC) guidelines on the use of unlicensed medicines and just 17% felt very comfortable prescribing an unlicensed medication when a licensed alternative was available. Key physician concerns included the lack of safety data (76%), legal implications (76%), and safety monitoring associated with unlicensed medicine use (71%). Patients and physicians agreed that safety and efficacy are the most important prescribing considerations, although 48% of participating physicians were worried that budget pressures may increase pressure to prescribe unlicensed medications on the basis of cost. A high proportion of patients (81%) also indicated some degree of concern, were they to be prescribed an unlicensed medication when a licensed alternative was available specifically because it costs less.Conclusions: This UK-based questionnaire study suggests pervasive concerns among prescribers over the safety, monitoring, and legal implications of unlicensed prescribing. High levels of concern were expressed among patients and physicians if cost were to become an influential factor when making decisions between licensed and unlicensed medications.Keywords: patient, physician, unlicensed treatment, concern, safety, trust
Dynamic Chromatin Organization during Foregut Development Mediated by the Organ Selector Gene PHA-4/FoxA
Tala H. I. Fakhouri,Jeff Stevenson,Andrew D. Chisholm,Susan E. Mango
PLOS Genetics , 2010, DOI: 10.1371/journal.pgen.1001060
Abstract: Central regulators of cell fate, or selector genes, establish the identity of cells by direct regulation of large cohorts of genes. In Caenorhabditis elegans, foregut (or pharynx) identity relies on the FoxA transcription factor PHA-4, which activates different sets of target genes at various times and in diverse cellular environments. An outstanding question is how PHA-4 distinguishes between target genes for appropriate transcriptional control. We have used the Nuclear Spot Assay and GFP reporters to examine PHA-4 interactions with target promoters in living embryos and with single cell resolution. While PHA-4 was found throughout the digestive tract, binding and activation of pharyngeally expressed promoters was restricted to a subset of pharyngeal cells and excluded from the intestine. An RNAi screen of candidate nuclear factors identified emerin (emr-1) as a negative regulator of PHA-4 binding within the pharynx, but emr-1 did not modulate PHA-4 binding in the intestine. Upon promoter association, PHA-4 induced large-scale chromatin de-compaction, which, we hypothesize, may facilitate promoter access and productive transcription. Our results reveal two tiers of PHA-4 regulation. PHA-4 binding is prohibited in intestinal cells, preventing target gene expression in that organ. PHA-4 binding within the pharynx is limited by the nuclear lamina component EMR-1/emerin. The data suggest that association of PHA-4 with its targets is a regulated step that contributes to promoter selectivity during organ formation. We speculate that global re-organization of chromatin architecture upon PHA-4 binding promotes competence of pharyngeal gene transcription and, by extension, foregut development.
Compounds from Silicones Alter Enzyme Activity in Curing Barnacle Glue and Model Enzymes
Daniel Rittschof,Beatriz Orihuela,Tilmann Harder,Shane Stafslien,Bret Chisholm,Gary H. Dickinson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016487
Abstract: Attachment strength of fouling organisms on silicone coatings is low. We hypothesized that low attachment strength on silicones is, in part, due to the interaction of surface available components with natural glues. Components could alter curing of glues through bulk changes or specifically through altered enzyme activity.
Improving the outcomes of primary care attenders with common mental disorders in developing countries: a cluster randomized controlled trial of a collaborative stepped care intervention in Goa, India
Vikram H Patel, Betty R Kirkwood, Sulochana Pednekar, Ricardo Araya, Michael King, Daniel Chisholm, Gregory Simon, Helen Weiss
Trials , 2008, DOI: 10.1186/1745-6215-9-4
Abstract: A cluster randomized controlled trial will be implemented in the state of Goa, on the west coast of India. Twenty-four primary care facilities, 12 from the government sector and 12 from the private sector, will be enrolled in two consecutive phases. For each sector, facilities will be randomly allocated within strata defined by urban/rural location, population size and presence of a visiting psychiatrist. Facilities will be randomly allocated to receive the collaborative stepped care intervention or the enhanced usual care control intervention. Both arms share two components of the intervention, viz., routine screening, and in the government clinics provision of antidepressants. In addition, the collaborative stepped care arm also provides a range of psychosocial treatments delivered by a specially trained Health Counselor, and supervision by a visiting Psychiatrist. A total of 3600 primary care attenders who are detected to suffer from a CMD based on a validated screening questionnaire will be recruited. The primary outcome is the proportion of subjects who recover from an ICD10 defined CMD at baseline by 6 months. Additional endpoints at 2 and 12 months will assess the speed and sustainability of achieving the primary outcomes. Other outcomes will include recovery from ICD10 defined depression and incidence of ICD-10 among individuals who were sub-threshold cases at baseline. Economic and disability outcomes will be assessed to estimate incremental cost-effectiveness ratios.This will be the first trial of the effectiveness of a complex intervention aiming to integrate efficacious treatments for CMD into routine primary care in a developing country. If effective, its findings will have relevance to policy makers who wish to scale up treatments for CMD in primary care across the world, but mostly in those countries where specialist mental health services are few.The MANAS project is registered through the National Institutes of Health sponsored clinical trials regis
Medical and Obstetric Complications among Pregnant Women Aged 45 and Older
Chad A. Grotegut, Christian A. Chisholm, Lauren N. C. Johnson, Haywood L. Brown, R. Phillips Heine, Andra H. James
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096237
Abstract: Objective The number of women aged 45 and older who become pregnant is increasing. The objective of this study was to estimate the risk of medical and obstetric complications among women aged 45 and older. Methods The Nationwide Inpatient Sample was used to identify pregnant woman during admission for delivery. Deliveries were identified using International Classification of Diseases, Ninth Revision (ICD-9-CM) codes. Using ICD-9-CM codes, pre-existing medical conditions and medical and obstetric complications were identified in women at the time of delivery and were compared for women aged 45 years and older to women under age 35. Outcomes among women aged 35–44 were also compared to women under age 35 to determine if women in this group demonstrated intermediate risk between the older and younger groups. Logistic regression analyses were used to calculate odds ratios with 95% confidence intervals for pre-existing medical conditions and medical and obstetric complications for both older groups relative to women under 35. Multivariable logistic regression analyses were also developed for outcomes at delivery among older women, while controlling for pre-existing medical conditions, multiple gestation, and insurance status, to determine the effect of age on the studied outcomes. Results Women aged 45 and older had higher adjusted odds for death, transfusion, myocardial infarction/ischemia, cardiac arrest, acute heart failure, pulmonary embolism, deep vein thrombosis, acute renal failure, cesarean delivery, gestational diabetes, fetal demise, fetal chromosomal anomaly, and placenta previa compared to women under 35. Conclusion Pregnant women aged 45 and older experience significantly more medical and obstetric complications and are more likely to die at the time of a delivery than women under age 35, though the absolute risks are low and these events are rare. Further research is needed to determine what associated factors among pregnant women aged 45 and older may contribute to these findings.
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