1,068 research outputs found
Wellcome Witnesses to Twentieth Century Medicine: Volume 1
Annotated and edited transcript of four Witness Seminars. Introduction by E M Tansey First published by the Wellcome Trust, 1997. ©The Trustee of the Wellcome Trust, London, 1997.In Volume One (Occasional Publication no. 4, 1997).All volumes are freely available online at: www.history.qmul.ac.uk/research/modbiomed/wellcome_witnesses/Annotated and edited transcript of four Witness Seminars. Introduction by E M Tansey.Annotated and edited transcript of four Witness Seminars. Introduction by E M Tansey.Annotated and edited transcript of four Witness Seminars. Introduction by E M Tansey.Annotated and edited transcript of four Witness Seminars. Introduction by E M Tansey.Four Witness Seminar transcripts of meetings held between 1993 and 1996: âTechnology Transfer in Britain: The case of Monoclonal Antibodiesâ (E M Tansey and P P Catterall, eds); âSelf and Non-Self: A History of Autoimmunityâ (E M Tansey, S V Willhoft and D A Christie, eds); âEndogenous Opiatesâ (E M Tansey and D A Christie, eds); âThe Committee on Safety of Drugsâ (E M Tansey and L A Reynolds, eds). Introduction by E M Tansey, âWhat is a Witness Seminarâ, separate index for each meeting. Tansey E M, Catterall P P, Christie D A, Willhoft S V, Reynolds L A. (eds) (1997) Wellcome Witnesses to Twentieth Century Medicine, volume 1. London: The Wellcome Trust.The Wellcome Trust is a registered charity, no. 210183
Heating Hot Atmospheres with Active Galactic Nuclei
High resolution X-ray spectroscopy of the hot gas in galaxy clusters has
shown that the gas is not cooling to low temperatures at the predicted rates of
hundreds to thousands of solar masses per year. X-ray images have revealed
giant cavities and shock fronts in the hot gas that provide a direct and
relatively reliable means of measuring the energy injected into hot atmospheres
by active galactic nuclei (AGN). Average radio jet powers are near those
required to offset radiative losses and to suppress cooling in isolated giant
elliptical galaxies, and in larger systems up to the richest galaxy clusters.
This coincidence suggests that heating and cooling are coupled by feedback,
which suppresses star formation and the growth of luminous galaxies. How jet
energy is converted to heat and the degree to which other heating mechanisms
are contributing, eg. thermal conduction, are not well understood. Outburst
energies require substantial late growth of supermassive black holes. Unless
all of the approximately 10E62 erg required to suppress star formation is
deposited in the cooling regions of clusters, AGN outbursts must alter
large-scale properties of the intracluster medium.Comment: 60 pages, 12 figures, to appear in 1997 Annual Reviews of Astronomy
and Astrophysics. This version supersedes the April 2007 version in Reviews
in Advance (references and minor corrections were added), and is similar to
the one scheduled to appear in Volume 45 of ARA
Randomized pharmacokinetic and pharmacodynamic comparison of fluoroquinolones for tuberculous meningitis.
Tuberculous meningitis (TBM) is the most lethal form of tuberculosis, and new treatments that improve outcomes are required. We randomly assigned adults with TBM to treatment with standard antituberculosis treatment alone or in combination with ciprofloxacin (750 mg/12 h), levofloxacin (500 mg/12 h), or gatifloxacin (400 mg/24 h) for the first 60 days of therapy. Fluoroquinolone concentrations were measured with plasma and cerebrospinal fluid (CSF) specimens taken at predetermined, randomly assigned times throughout treatment. We aimed to describe the pharmacokinetics of each fluoroquinolone during TBM treatment and evaluate the relationship between drug exposure and clinical response over 270 days of therapy (Controlled Trials number ISRCTN07062956). Sixty-one patients with TBM were randomly assigned to treatment with no fluoroquinolone (n = 15), ciprofloxacin (n = 16), levofloxacin (n = 15), or gatifloxacin (n = 15). Cerebrospinal fluid penetration, measured by the ratio of the plasma area under the concentration-time curve from 0 to 24 h (AUC0â24) to the cerebrospinal fluid AUC0â24, was greater for levofloxacin (median, 0.74; range, 0.58 to 1.03) than for gatifloxacin (median, 0.48; range, 0.47 to 0.50) or ciprofloxacin (median, 0.26; range, 0.11 to 0.77). Univariable and multivariable analyses of fluoroquinolone exposure against a range of different treatment responses revealed worse outcomes among patients with lower and higher plasma and CSF exposures than for patients with intermediate exposures (a U-shaped exposure-response). TBM patients most likely to benefit from fluoroquinolone therapy were identified, along with exposure-response relationships associated with improved outcomes. Fluoroquinolones add antituberculosis activity to the standard treatment regimen, but to improve outcomes of TBM, they must be started early, before the onset of coma
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Reflective Journaling: A Theoretical Model and Digital Prototype for Developing Resilience and Creativity
Reflection is commonly discussed as a tool for personal and professional development that is becoming increasingly important in todayâs global and digital world. In this paper, we propose a model that suggests ways in which reflection, in the form of Reflective Journaling, can support the development of creativity and resilience, which are needed to enable individuals to function effectively in a fast-changing environment. In addition, the model proposes ways in which external support and progress monitoring can be used in conjunction with skills in adaptive resilience and structured creativity, to support the maintenance of reflective journaling as a habit, in the longer term, thus creating virtuous cycles of skills and behaviours that can reinforce each other. Based on our model, and additional user research, we describe the design of a first digital prototype that aims to support the use of Reflective Journaling and to develop creativity and resilience through suggested mechanisms. Initial evaluations of our prototype are positive. It has been well-received by early test users, and has the potential to address all the connections defined. We therefore suggest that the theoretical model can be used to develop digital tools, such as the one included, to help those who wish to develop the habit of reflective journaling, and through that a range of other skills associated with resilience and creative thinking. We see this as a starting point for investigating this potential in more depth
Pericyte FAK negatively regulates Gas6/Axl signalling to suppress tumour angiogenesis and tumour growth
The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement in angiogenesis and tumour growth, but how pericyte FAK regulates tumour angiogenesis is unknown. We show that pericyte FAK regulates tumour growth and angiogenesis in multiple mouse models of melanoma, lung carcinoma and pancreatic B-cell insulinoma and provide evidence that loss of pericyte FAK enhances Gas6-stimulated phosphorylation of the receptor tyrosine kinase, Axl with an upregulation of Cyr61, driving enhanced tumour growth. We further show that pericyte derived Cyr61 instructs tumour cells to elevate expression of the proangiogenic/protumourigenic transmembrane receptor Tissue Factor. Finally, in human melanoma we show that when 50% or more tumour blood vessels are pericyte-FAK negative, melanoma patients are stratified into those with increased tumour size, enhanced blood vessel density and metastasis. Overall our data uncover a previously unknown mechanism of tumour growth by pericytes that is controlled by pericyte FAK
Ciliated Epithelial Cell Differentiation at Air-Liquid Interface Using Commercially Available Culture Media
The human nasal epithelium contains basal stem/progenitor cells that produce differentiated multiciliated and mucosecretory progeny. Basal epithelial cells can be expanded in cell culture and instructed to differentiate at an air-liquid interface using transwell membranes and differentiation media. For basal cell expansion, we have used 3T3-J2 co-culture in epithelial culture medium containing EGF, insulin, and a RHO-associated protein kinase (ROCK) inhibitor, Y-27632 (3T3 + Y). Here we describe our protocols for ciliated differentiation of these cultures at air-liquid interface and compare four commercially available differentiation media, across nine donor cell cultures (six healthy, two patients with chronic obstructive pulmonary disease (COPD), and one with primary ciliary dyskinesia (PCD)). Bright-field and immunofluorescence imaging suggested broad similarity between differentiation protocols. Subtle differences were seen in transepithelial electrical resistance (TEER), ciliary beat frequency, mucus production, and the extent to which basal cells are retained in differentiated cultures. Overall, the specific differentiation medium used in our air-liquid interface culture protocol was not a major determinant of ciliation, and our data suggest that the differentiation potential of basal cells at the outset is a more critical factor in air-liquid interface culture outcome. Detailed information on the constituents of the differentiation media was only available from one of the four manufacturers, a factor that may have profound implications in the interpretation of some research studies
Doubleâblind control of the data manager doesn't have any impact on data entry reliability and should be considered as an avoidable cost
<p>Abstract</p> <p>Background</p> <p>Database systems have been developed to store data from large medical trials and survey studies. However, a reliable data storage system does not guarantee data entering reliability.</p> <p>We aimed to evaluate if double-blind control of the data manager might have any effect on data-reliability. Our secondary aim was to assess the influence of the inserting position in the insertion-sheet on data-entry accuracy and the effectiveness of electronic controls in identifying data-entering mistakes.</p> <p>Methods</p> <p>A cross-sectional survey and single data-manager data entry.</p> <p>Data from PACMeR_02 survey, which had been conducted within a framework of the SESy-Europe project (PACMeR_01.4), were used as substrate for this study. We analyzed the electronic storage of 6446 medical charts. We structured data insertion in four sequential phases. After each phase, the data stored in the database were tested in order to detect unreliable entries through both computerized and manual random control. Control was provided in a double blind fashion.</p> <p>Results</p> <p>Double-blind control of the data manager didn't improve data entry reliability. Entries near the end of the insertion sheet were correlated with a larger number of mistakes. Data entry monitoring by electronic-control was statistically more effective than hand-searching of randomly selected medical records.</p> <p>Conclusion</p> <p>Double-blind control of the data manager should be considered an avoidable cost. Electronic-control for monitoring of data-entry reliability is suggested.</p
Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us
Supernova remnants (SNRs) arise from the interaction between the ejecta of a
supernova (SN) explosion and the surrounding circumstellar and interstellar
medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However,
to understand SNRs as a whole, large samples of SNRs must be assembled and
studied. Here, we describe the radio, optical, and X-ray techniques which have
been used to identify and characterize almost 300 Galactic SNRs and more than
1200 extragalactic SNRs. We then discuss which types of SNRs are being found
and which are not. We examine the degree to which the luminosity functions,
surface-brightness distributions and multi-wavelength comparisons of the
samples can be interpreted to determine the class properties of SNRs and
describe efforts to establish the type of SN explosion associated with a SNR.
We conclude that in order to better understand the class properties of SNRs, it
is more important to study (and obtain additional data on) the SNRs in galaxies
with extant samples at multiple wavelength bands than it is to obtain samples
of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by
Athem W. Alsabti and Paul Murdin. Final version available at
https://doi.org/10.1007/978-3-319-20794-0_90-
Entrepreneurship, export orientation and economic growth
In this paper the relationship between a countryâs prevalence of new ventures and its rate of economic growth is investigated, while taking into account new venturesâ export orientation. It is generally acknowledged that new venture creation as well as export activity may both be important strategies for achieving national economic growth. However, to our knowledge no attempt has been made to investigate empirically the role of export-driven new ventures in economic growth. We focus on the national level and use data for a sample of 34 countries over the period 2002â2008. Our results suggest that, on top of a positive relation between entrepreneurial activity in general and subsequent macroeconomic growth, there is an additional positive effect of export-oriented early-stage entrepreneurship in higher-income countries. However, there is no such additional effect in lower-income countries
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