541 research outputs found
The Arms Trade in Russian-Chinese Relations: Identity, domestic politics, and geopolitical positioning
Soluble Mediators, Not Cilia, Determine Airway Surface Liquid Volume in Normal and Cystic Fibrosis Superficial Airway Epithelia
A key aspect of the lung's innate defense system is the ability of the superficial epithelium to regulate airway surface liquid (ASL) volume to maintain a 7-Ī¼m periciliary liquid layer (PCL), which is required for cilia to beat and produce mucus flow. The mechanisms whereby airway epithelia regulate ASL height to ā„7 Ī¼m are poorly understood. Using bumetanide as an inhibitor of Clā secretion, and nystatin as an activator of Na+ absorption, we found that a coordinated āblendingā of both Clā secretion and Na+ absorption must occur to effect ASL volume homeostasis. We then investigated how ASL volume status is regulated by the underlying epithelia. Cilia were not critical to this process as (a) ASL volume was normal in cultures from patients with primary ciliary dyskinesia with immotile cilia, and (b) in normal cultures that had not yet undergone ciliogenesis. However, we found that maneuvers that mimic deposition of excess ASL onto the proximal airways, which occurs during mucociliary clearance and after glandular secretion, acutely stimulated Na+ absorption, suggesting that volume regulation was sensitive to changes in concentrations of soluble mediators in the ASL rather than alterations in ciliary beating. To investigate this hypothesis further, we added potential āsoluble mediatorsā to the ASL. ASL volume regulation was sensitive to a channel-activating protein (CAP; trypsin) and a CAP inhibitor (aprotinin), which regulated Na+ absorption via changes in epithelial Na+ channel (ENaC) activity in both normal and cystic fibrosis cultures. ATP was also found to acutely regulate ASL volume by inducing secretion in normal and cystic fibrosis (CF) cultures, while its metabolite adenosine (ADO) evoked secretion in normal cultures but stimulated absorption in CF cultures. Interestingly, the amount of ASL/Clā secretion elicited by ATP/ADO was influenced by the level of CAP-induced Na+ absorption, suggesting that there are important interactions between the soluble regulators which finely tune ASL volume
Exotic Differentiable Structures and General Relativity
We review recent developments in differential topology with special concern
for their possible significance to physical theories, especially general
relativity. In particular we are concerned here with the discovery of the
existence of non-standard (``fake'' or ``exotic'') differentiable structures on
topologically simple manifolds such as , \R and
Because of the technical difficulties involved in the smooth case, we begin
with an easily understood toy example looking at the role which the choice of
complex structures plays in the formulation of two-dimensional vacuum
electrostatics. We then briefly review the mathematical formalisms involved
with differentiable structures on topological manifolds, diffeomorphisms and
their significance for physics. We summarize the important work of Milnor,
Freedman, Donaldson, and others in developing exotic differentiable structures
on well known topological manifolds. Finally, we discuss some of the geometric
implications of these results and propose some conjectures on possible physical
implications of these new manifolds which have never before been considered as
physical models.Comment: 11 pages, LaTe
Numerical Calabi-Yau metrics
We develop numerical methods for approximating Ricci flat metrics on
Calabi-Yau hypersurfaces in projective spaces. Our approach is based on finding
balanced metrics, and builds on recent theoretical work by Donaldson. We
illustrate our methods in detail for a one parameter family of quintics. We
also suggest several ways to extend our results.Comment: 23 pages, 3 figure
Isolated angioedema of the bowel due to C1 esterase inhibitor deficiency: a case report and review of literature
<p>Abstract</p> <p>Introduction</p> <p>We report a rare, classic case of isolated angioedema of the bowel due to C1-esterase inhibitor deficiency. It is a rare presentation and very few cases have been reported worldwide. Angioedema has been classified into three categories.</p> <p>Case presentation</p> <p>A 66-year-old Caucasian man presented with a ten-month history of episodic severe cramping abdominal pain, associated with loose stools. A colonoscopy performed during an acute attack revealed nonspecific colitis. Computed tomography of the abdomen performed at the same time showed a thickened small bowel and ascending colon with a moderate amount of free fluid in the abdomen. Levels of C4 (< 8 mg/dL; reference range 15 to 50 mg/dL), CH50 (< 10 U/mL; reference range 29 to 45 U/ml) and C1 inhibitor (< 4 mg/dL; reference range 14 to 30 mg/dL) were all low, supporting a diagnosis of acquired angioedema with isolated bowel involvement. Our patient's symptoms improved with antihistamine and supportive treatment.</p> <p>Conclusion</p> <p>In addition to a detailed comprehensive medical history, laboratory data and imaging studies are required to confirm a diagnosis of angioedema due to C1 esterase inhibitor deficiency.</p
The social value of a QALY : raising the bar or barring the raise?
Background: Since the inception of the National Institute for Health and Clinical Excellence (NICE) in England,
there have been questions about the empirical basis for the cost-per-QALY threshold used by NICE and whether
QALYs gained by different beneficiaries of health care should be weighted equally. The Social Value of a QALY
(SVQ) project, reported in this paper, was commissioned to address these two questions. The results of SVQ were
released during a time of considerable debate about the NICE threshold, and authors with differing perspectives
have drawn on the SVQ results to support their cases. As these discussions continue, and given the selective use of
results by those involved, it is important, therefore, not only to present a summary overview of SVQ, but also for
those who conducted the research to contribute to the debate as to its implications for NICE.
Discussion: The issue of the threshold was addressed in two ways: first, by combining, via a set of models, the
current UK Value of a Prevented Fatality (used in transport policy) with data on fatality age, life expectancy and
age-related quality of life; and, second, via a survey designed to test the feasibility of combining respondentsā
answers to willingness to pay and health state utility questions to arrive at values of a QALY. Modelling resulted in
values of Ā£10,000-Ā£70,000 per QALY. Via survey research, most methods of aggregating the data resulted in values
of a QALY of Ā£18,000-Ā£40,000, although others resulted in implausibly high values. An additional survey, addressing
the issue of weighting QALYs, used two methods, one indicating that QALYs should not be weighted and the
other that greater weight could be given to QALYs gained by some groups.
Summary: Although we conducted only a feasibility study and a modelling exercise, neither present compelling
evidence for moving the NICE threshold up or down. Some preliminary evidence would indicate it could be
moved up for some types of QALY and down for others. While many members of the public appear to be open to
the possibility of using somewhat different QALY weights for different groups of beneficiaries, we do not yet have
any secure evidence base for introducing such a system
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